Purification of real car wash wastewater with complex coagulation/flocculation methods using polyaluminum chloride, polyelectrolyte, clay mineral and cationic surfactant.

In the present study, real car wash wastewater was purified by different coagulation/flocculation methods. As coagulant, polyaluminum chloride ('BOPAC'), conventional iron(III) chloride, iron(III) sulfate, and aluminum(III) chloride were used, while as flocculant non-ionic and anionic polyelectrolytes were investigated. The effects of added clay mineral (Na-bentonite) and cationic surfactant (hexadecyltrimethyl ammonium bromide - 'HTABr') were also investigated. The use of BOPAC was significantly more effective than conventional coagulants. Extra addition of clay mineral was also beneficial in relation to both the sediment volume and sedimentation speed, while polyelectrolyte addition enhanced further the sedimentation. Moreover, the simultaneous addition of HTABr significantly enhanced the color removal efficiency due to the successful in-situ generation of organophilic bentonite. In summary, the application of 100 mg L-1 Na-bentonite with 20 mg L-1 Al3+ (from BOPAC) and 0.5 mg L-1 anionic polyelectrolyte resulted in the efficient reduction of the turbidity (4-6 NTU), the COD (158 mg L-1) and the extractable oil content (4 mg L-1) with efficiencies of 98%, 59%, and 85%, respectively. By applying organophilic bentonite in high concentration (500 mg L-1) with identical concentrations of BOPAC and anionic polyelectrolyte, significant color removal (5 times lower absorbance at λ = 400 nm) and 27% lower sediment volume were achieved.

The paradox of the binomial Ixodes ricinus activity and the observed unimodal Lyme borreliosis season in Hungary.

The change of ambient temperature plays a key role in determining the run of the annual Lyme season. Our aim was to explain the apparent contradiction between the annual unimodal Lyme borreliosis incidence and the bimodal Ixodes ricinus tick activity run--both observed in Hungary--by distinguishing the temperature-dependent seasonal human and tick activity, the temperature-independent factors, and the multiplicative effect of human outdoor activity in summer holiday, using data from Hungary in the period of 1998-2012. This separation was verified by modeling the Lyme incidence based on the separated factors, and comparing the run of the observed and modeled incidence. We demonstrated the bimodality of tick season by using the originally unimodal Lyme incidence data. To model the outdoor human activity, the amount of camping guest nights was used, which showed an irregular run from mid-June to September. The human outdoor activity showed a similar exponential correlation with ambient temperature to that what the relative incidence did. It was proved that summer holiday has great influence on Lyme incidence.

A pilot study of Cerasorb and Bio-Oss enhanced new bone formation in animal model.

The aim of this pilot investigation was to develop a new animal model for studying the effects on osteogenesis of agents used in the guided bone regeneration technique. As test material, a mixture of two osseoconductive materials with different physico-chemical characteristics was used. One component of the mixture was Bio-Oss, a bovine hydroxyapatite; the other was Cerasorb, a synthetic tricalcium phosphate. The mixture consisited of 50 volume percent of Bio-Oss and 50 volume percent of Cerasorb. In in vivo pilot experiment, bone wounds were prepared in the proximal third of both femurs of rabbits. A Cerasorb + Bio-Oss mixture was inserted on the test side and the same amount of sterile buffered physiological solution on the control side. After healing for 4 weeks, the bone segments were embedded and cut without decalcification, using the Exact cutting and grinding system. The density of the newly-formed bone was evaluated histomorphometrically. On the Cerasorb + Bio-Oss test side the bone density was almost 1.5 times higher than that on the control side. These results demonstrated that the applied animal model is appropriate for investigation of the effects on osteogenesis of biocompatible graft materials such as Bio-Oss and Cerasorb.

Macromolecular binding of glucocorticoids in human mammary carcinoma.

The presence of glucocorticoid receptors was examined in 100 primary and 22 metastatic human breast cancer lesions. Aliquots of cytosol were incubated in vitro with tritiated cortisol and dexamethasone with and without competing steroids. Two different types of glucocorticoid receptors were detected. One is similar to transcortin; it sediments at 4 S in the ultracentrifuge, has a dissociation constant in the same range (10(-8) M), and does not bind fluorinated corticosteroids. While every tumor showed cortisol binding, very high activity (greater than 1000 fmoles/g tissue) was detected in 38% of primaries and in 59% of metastases. Plasma transcortin could be excluded as the source of binding activity. The other receptor binds both natural and fluorinated corticosteroids, has a higher affinity (Kd 10(-9) M), and sediments at 8 S. It was present in 23% of tumors and its quantity (26 to 995 fmoles/g) was much less than that of cortisol binder (50 to 6000 fmoles/g). While there was no correlation between the two glucocorticoid receptors, 80% of dexamethasone receptor-positive cases also had estrogen receptor. The results indicate that a significant proportion of these tumors could be subject to glucocorticoid influence.

Cortisol in human breast cancer tissue.

Endogenous cortisol levels were measured by radioimmunoassay in 140 primary and 31 metastatic human breast cancer specimens. The adjacent normal breast was assayed in 15 cases. Mean values for normal breast were 17.3 ng/g tissue. Significantly higher levels were found in cancer tissue. Primary lesions contained 26 ng/g and metastases 32.5 ng/g cortisol. These results lend support to our previous data on increased cortisol binding activity in human breast cancer.

Intranasal and subcutaneous treatment of central precocious puberty in both sexes with a long-acting analog of luteinizing hormone-releasing hormone.

The chronic administration of the long-acting LHRH agonist analog D-Ser(TBU)6-LHRH-EA10 (HOE 766, Buserelin) suppresses pituitary gonadotropin secretion. Since a similar analog was shown to be effective in the short term parenteral treatment of idiopathic precocious puberty in girls (10), we used Buserelin both intranasally and sc to treat patients of both sexes with idiopathic and secondary central precocious puberty to test its efficacy, safety, and potential for long term use. Six girls and two boys presented with advanced skeletal maturity, accelerated growth velocity, Tanner stage II-IV pubertal development, and pubertal levels of sex steroids and gonadotropins. Patients were treated for 6 months sc and up to 5 months intranasally. Optimal doses ranged from 10-20 micrograms/kg X day in girls and 30 micrograms/kg X day in boys, with marked individual variation. During sc therapy, there was significant suppression of growth velocity (P less than 0.001), serum gonadotropins (P less than 0.001), 17 beta-estradiol (P less than 0.005), and testosterone as well as clinical and behavioral improvement. The rate of bone maturation was reduced. All effects were reversed after discontinuation of therapy for 1 month in one girl. No reduction in efficacy was seen after changing four girls and one boy to intranasal therapy, but improved acceptability and compliance were reported by parents. Apart from withdrawal bleeding in one girl and transient acceleration of puberty in two patients during the initial phase of treatment, no serious unwanted effects occurred. Antibodies to native LHRH were not detected after 6 months of therapy. These results confirm the efficacy and safety of Buserelin by intranasal and sc routes in patients with sexual precocity and indicate a need for long term studies.

Dose finding, placebo-controlled study of oral almotriptan in the acute treatment of migraine.

OBJECTIVE: To assess the efficacy and tolerability of oral almotriptan, a selective serotonin receptor (5-HT1B/1D) agonist, when used at different doses in the treatment of acute migraine. METHODS: This was a placebo controlled, double-blind, parallel-group, dose-finding study. Patients satisfying International Headache Society criteria for acute migraine were randomized to a single dose of placebo or oral almotriptan 2, 6.25, 12.5, or 25 mg at the onset of moderate or severe pain. Patients graded pain intensity on a 4-point verbal scale from 0 (no pain) to 3 (severe pain) and recorded adverse events. The primary efficacy variable was headache response at 2 hours. Data were analyzed on an intent-to-treat basis. RESULTS: Nine hundred and three patients were randomized, and 742 were included in the evaluation of the efficacy and tolerability. Headache response at 2 hours was 32.5% with placebo, and 30%, 56.3%, 58.5%, and 66.5% with almotriptan 2, 6.25, 12.5, and 25 mg doses (p < 0.05 for 6.25, 12.5, and 25 mg vs placebo). A dose-dependent decrease in the incidence of migraine-associated symptoms and the need for escape medication was observed. The incidence of adverse events with the almotriptan 2-mg, 6.25-mg, and 12.5-mg groups was comparable to that with the placebo group. CONCLUSION: Almotriptan 12.5 mg demonstrated the most favorable ratio between efficacy and tolerability, offering equivalent efficacy and better tolerability compared with the 25 mg dose. The minimum effective dose of almotriptan was 6.25 mg.

Protective effects of mercaptoethylguanidine, a selective inhibitor of inducible nitric oxide synthase, in ligature-induced periodontitis in the rat.

1. Excessive production of nitric oxide (NO), and the generation of peroxynitrite have been implicated in various proinflammatory conditions. In the present study, using mercaptoethylguanidine (MEG), a selective inhibitor of iNOS and a peroxynitrite scavenger, we investigated the role of iNOS and peroxynitrite in a rat model of periodontitis. 2. Periodontitis was produced in rat by a ligature of 2/0 braided silk placed around the cervix of the lower left 1st molar. Animals were then divided into two groups: one group of rats was treated with MEG (30 mg kg(-1), i.p., 4 times per day for 8 days), animals in the other group received vehicle. At day 8, the gingivomucosal tissue encircling the mandibular 1st molars was removed on both sides from ligated and sham operated animals for inducible nitric oxide synthase (iNOS) activity assay and for immunocytochemistry with anti-iNOS serum. Plasma extravasation was measured with the Evans blue technique. Alveolar bone loss was measured with a videomicroscopy. 3. Ligation caused a significant, more than 3 fold increase in the gingival iNOS activity, whereas it did not affect iNOS activity on the contralateral side, when compared to sham-operated animals. Immunohistochemical analysis revealed iNOS-positive macrophages, lymphocytes and PMNs in the connective tissue and immunoreactive layers of epithelium on side of the ligature, and only a few iNOS reactive connective tissue cells on the contralateral side [corrected]. Ligation significantly increased Evans blue extravasation in gingivomucosal tissue and alveolar bone destruction compared to the contralateral side. MEG treatment significantly reduced the plasma extravasation and bone destruction. 4. The present results demonstrated that ligature-induced periodontitis increases local NO production and that MEG treatment protects against the associated extravasation and bone destruction. Based on the present data, we propose that enhanced formation of NO and peroxynitrite plays a significant role in the pathogenesis of periodontitis.

Genetic differences in the cortisol concentration of the adrenal and other tissues of white and coloured guinea-pigs.

The effect of genetic difference (white v. coloured) on the cortisol content of ten different organs and tissues, including the adrenals, of white and coloured guinea-pigs of both sexes and of different ages was studied by protein-binding techniques. Tissue cortisol concentration was significantly higher in all the tissues and adrenals of white animals of both sexes compared with coloured animals. The difference in tissue cortisol content between white and coloured animals was higher before (range 41-5-134-1%) than after puberty (range 10-1--82-5%). The age-dependent decrease of cortisol concentration in different tissues and adrenals in adults was more marked in white guinea-pigs of both sexes (mean 30-6%, range 0-0--71-5%) than in coloured (mean 16-9%, range 0-0--63-1%. In adult animals the liver contained significantly (11-8--36-4%) more cortisol than in prepubertal animals. This pattern was the same in white and coloured guinea-pigs of both sexes.

Surface modifications induced by ns and sub-ps excimer laser pulses on titanium implant material.

Medical implants used in oral and orthopaedic surgery are mainly produced from titanium. Their biological behaviour, e.g. osseointegration, essentially depends on both the chemical composition and the morphology of the surface. Modifications achieved by excimer laser irradiation of titanium samples were investigated in order to improve their surface characteristics so as to facilitate biointegration. To enlarge the effective interfacial area of bone-implant contact, holes were ablated by laser pulses of ns or sub-ps length. During ns ablation, crown-like projecting rims formed around the borders of the holes. Ultra-short (0.5ps) KrF excimer laser pulses were successfully applied to avoid these undesirable formations. Since a smooth dental implant surface is necessary to maintain a healthy connection with the soft tissues, laser polishing of samples was investigated, too. Irradiation with a series of ns laser pulses resulted in effective smoothing, as measured with atomic force microscope. X-ray photoelectron spectroscopy analysis of the laser-polished titanium surface revealed that laser treatment led to a decrease of the surface contamination and in thickening of the oxide layer. X-ray diffraction measurements demonstrated that the original alpha-titanium crystal structure was preserved.

VIP and noncholinergic vasodilatation in rabbit submandibular gland.

The effect of parasympathetic nerve activation on rabbit submandibular gland (SMG) blood flow and saliva secretion were studied before and after systemic administration of atropine or hexamethonium. The parasympathetic fibers were stimulated electrically (2 and 15 Hz, 10 V, 1 msec) at the plexus around the submandibular salivary duct or at the chorda lingual nerve. In untreated animals, stimulation of parasympathetic fibers caused a frequency-dependent increase of salivary secretion and blood flow in the SMG. Atropine treatment completely abolished saliva secretion at 2 Hz and 15 Hz and the increase in SMG blood flow during stimulation at 2 Hz. Although atropine significantly reduced the vasodilatory response at 15 Hz, the highest blood flow measured under such circumstances was still about 2.5 times the prestimulation value. After hexamethonium administration no blood flow increase or saliva secretion was seen upon chorda lingual stimulation. The concentration of vasoactive intestinal polypeptide (VIP)-like immunoreactivity in the venous effluent of the SMG increased during nerve stimulation. Atropine significantly reduced, and hexamethonium abolished this VIP-output elicited by parasympathetic nerve stimulation. Local infusion of VIP, peptide histidine isoleucine (PHI) and substance P all caused atropine-resistant vasodilation but no salivation. The present data suggest that VIP and possibly PHI play a role in the atropine-resistant vasodilatation in rabbit submandibular gland elicited by parasympathetic nerve stimulation. The contribution of sensory mediators such as substance P released by stimulation of afferent nerves in the chorda lingual nerve to the salivary and vasodilatory responses seems to be of minor importance in the rabbit submandibular gland.

Multiple sclerosis: failure of treatment with verapamil in a pilot trial.

Verapamil hydrochloride, a lipophilic calcium channel blocking agent was used in the treatment of 11 patients with multiple sclerosis. The rationale of the therapy was to improve the conduction capacity of the damaged nerve fibres. The therapy did not prove effective in a pilot trial.

Inhibition of ovulation during discontinuous intranasal luteinizing hormone-releasing hormone agonist dosing in combination with gestagen-induced bleeding.

Four groups of eight or nine normal cycling volunteers with regular menstrual cycles had daily blood sampling during two pretreatment, two treatment, and two posttreatment cycles. Intranasal doses of 100, 200, and 300 micrograms of (D-Ser[TBU]6-des-Gly-NH210) luteinizing hormone-releasing hormone (LH-RH) ethylamide were administered every 12 hours and compared with a 400-micrograms dose given every 24 hours during two periods of 21 days followed by a drug-free interval of 7 days. Five milligrams of medroxyprogesterone acetate was taken orally on days 17 to 21. Serum luteinizing hormone was elevated during the first 2 weeks of treatment, and serum follicle-stimulating hormone was increased only during the first 2 days of treatment. At 100 to 300 micrograms/12 hours serum estradiol was stimulated up to preovulatory levels, whereas at 400 micrograms/24 hours most values were in the early follicular phase range. Ovarian ultrasonography revealed the transient development of preovulatory-like follicles in 8 of 12 studied cycles. Serum progesterone values were less than 2 ng/ml in 57.3%, between 2 and 5 ng/ml in 27.9%, and greater than 5 ng/ml in 14.7%. Withdrawal bleeding occurred during the pause in 97% of treatment cycles. Nine of 13 breakthrough bleedings happened in the groups given 100-micrograms and 300-micrograms/12 hours. Recovery cycles showed slightly prolonged follicular phases with normal luteal phases. No changes were observed in routine laboratory measurements. In conclusion, intermittent administration of appropriate LH-RH agonist dosing in combination with a progestogen would effectively block ovulation while preserving adequate cyclic estradiol secretion and could be an alternative contraceptive approach.

PIP: 4 groups of 8 or 9 normal cycling volunteers with regular menstrual cycles had daily blood sampling during 2 pretreatment, 2 treatment, and 2 posttreatment cycles. Intranasal doses of 100, 200, and 300 mcg of luteninizing hormone-releasing hormone (LH-RH) ethylamide were administered every 12 hours and compared with a 400-mcg dose given every 24 hours during 2 periods of 21 days followed by a drug-free interval of 7 days. 5 milligrams of medroxyprogesterone acetate was taken orally on days 17 to 21. Serum luteinizing hormone was elevated during the first 2 weeks of treatment and serum follicle-stimulating hormone was increased only during the first 2 days of treatment. At 100-300 mg/12 hours serum estradiol was stimulated up to preovulatory levels, whereas at 400 mcg/24 hours most values were in the early follicular phase range. Ovarian ultrasonography revealed the transient development of preovulatory-like follicles in 8 of 12 studied cycles. Serum progesterone values were less than 2 ng/ml in 57.3%, between 2-5 ng/ml in 27.9%, and greater than 5 ng/ml in 14.7%. Withdrawal bleeding occurred during the pause in 97% of treatment cycles. 9 of 13 breakthrough bleedings happened in the groups given 100-mcg and 300-mcg/12 hours. Recovery cycles showed slightly prolonged follicular phases with normal luteal phases. No changes were observed in routine laboratory measurements. In conclusion, intermittent administration of appropriate LH-RH agonist dosing in combination with a progestogen would effectively block ovulation while preserving adequate cyclic estradiol secretion and could be an alternative contraceptive approach.

Gonadotroph and corpus luteum responses to two successive intranasal doses of a luteinizing hormone-releasing hormone agonist at different days after the midcycle luteinizing hormone surge.

Two successive intranasal doses (300 micrograms at 8:00 A.M. and 6:00 P.M.) of the luteinizing hormone-releasing hormone (LH-RH) agonist (D-Ser[TBU]6-des-Gly-NH2(10))LH-RH ethylamide (Buserelin) were administered on days 1 to 10 after the midcycle luteinizing hormone (LH) surge in 33 normally cycling women. Maximal stimulation of gonadotropins was observed at 4 hours and was of higher amplitude in the first 2 days after the LH surge. The response to the second dose was markedly blunted, showing pituitary refractoriness. On each day of treatment there was a progressive increase of serum estradiol, which was maximal (threefold) 4 hours after the second dose of Buserelin. Serum progesterone (P) levels were not significantly changed on days 1 to 4, but they were increased by 50% at 10 hours on days 5 to 10. Daily blood samples revealed that following treatment on days 1 to 4 after the midcycle LH surge, serum P profiles were lower than in control cycles, without change in the length of the luteal phase. Starting on treatment day 5, a precocious luteolysis was induced, as illustrated by an early fall in serum P levels and shortening of the luteal phase (1 to 4 days). All posttreatment control cycles were normal. The results of this time study indicate that an appropriate treatment with an intranasal Buserelin administered at any time between days 1 to 10 after the midcycle LH surge impair luteal function and could lead to a new postcoital contraceptive approach.

Reversible hypogonadism induced by a luteinizing hormone-releasing hormone (LH-RH) agonist (Buserelin) as a new therapeutic approach for endometriosis.

Ten women with endometriosis (stages I to IV) were treated with twice-daily subcutaneous injections of 200 micrograms of (D-Ser[TBU]6-des-Gly-NH2(10] luteinizing hormone-releasing hormone ethylamide (Buserelin) for 5 days followed by 400 micrograms intranasally three times daily for 25 to 31 weeks. Serum follicle-stimulating hormone levels returned to basal values on the second day of treatment, and serum luteinizing hormone levels progressively decreased to normal within 4 weeks. Serum estradiol decreased below early follicular phase levels within 7 to 30 days and continued to decrease to castrate levels. Light to moderate estrogen withdrawal bleeding was followed by amenorrhea with occasional bleeding or spotting in four women. Abdominal pain and dyspareunia disappeared or were ameliorated after 2 months of treatment. Resorption of endometrial implants was demonstrated by laparoscopy, and endometrial biopsy revealed atrophy or weak proliferation. Ovulation returned within 45 days, and two of four sexually active women became pregnant during cycles 3 and 5. The treatment was well accepted in spite of the expected hot flushes and vaginal dryness. Safety laboratory tests during and after treatment did not reveal any abnormalities. Reversible down-regulation of pituitary/ovarian function using repetitive luteinizing hormone-releasing hormone agonist administration can be a worthwhile approach to medical treatment of endometriosis.

Gonadotropins and estradiol responses to single intranasal or subcutaneous administration of a luteinizing hormone-releasing hormone agonist in the early follicular phase.

Single increasing intranasal and subcutaneous doses of a potent luteinizing hormone-releasing hormone (LH-RH) agonistic analog (D-Ser[TBU]6-des-Gly-NH2(10))LH-RH ethylamide (Buserelin) were administered on day 2 or 3 of the follicular phase in 59 normal women. Groups of five or six volunteers received intranasal doses ranging from 50 to 1300 micrograms and subcutaneous doses varying between 0.3 and 30 micrograms of the LH-RH agonist. Maximal amplitude of the serum gonadotropin response is observed at 6 hours. A sixfold increase is obtained for luteinizing hormone (LH) at a 200 micrograms intranasal dose, whereas maximal follicle-stimulating hormone (FSH) stimulation (threefold) is reached at a lower dose (100 micrograms). A 1000-micrograms dose elicits a more prolonged stimulation, levels of FSH and LH being two and five times above control levels at 11 hours. Similar response curves are obtained by the subcutaneous route, a maximal stimulation being reached at 3 micrograms for FSH and at 10 micrograms for LH. Serum estradiol levels are maximally increased at 11 hours after administration of 10 and 200 micrograms of the analog by the respective subcutaneous and intranasal routes. Twenty-four-hour response curves of gonadotropins indicate that the efficacy of the intranasal route is approximately 3% to 5% of the subcutaneous route. These observations should provide information useful in the investigation of the antifertility effects and medical treatments using an intranasal LH-RH agonist in the human being.

The application of immunofluorescent antibody method in research of human brain edema.

The direct and indirect immunofluorescent methods were used to demonstrate the serum proteins in vasogenic brain edema on paraffin embedded formalin fixed human brains with carcinoma metastases. Applying these techniques extravasated albumin was detected within the tumor and in the surrounding neuropil. In the remote part of the peritumorous area the cytoplasma of neurons and astrocytes were stained specifically. The specific immunostaining clearly demonstrates the plasma origin of proteins in human peritumorous edema similarly to the experimental vasogenic brain edema. The immunofluorescent technique seems to be very useful to investigate the human brain edema on necropsy material as well.

Effect of indomethacin on the blood flow of the rabbit submandibular gland.

Effects of the stimulation of the chorda tympani and acetylcholine infused into the artery of the gland were studied on the blood flow and saliva secretion of the rabbit submandibular gland before and after indomethacin treatment. The enhancement of blood flow and saliva secretion was less apparent after indomethacin than before. Results suggest that endogenous prostaglandins are also involved in the mechanism of the augmentation of blood flow and saliva secretion produced by the stimulation of the chorda tympani in the rabbit submandibular gland.

Effect of denervation on the neurogenic inflammation of the rat mandibular mucosa.

Effects of local exposure to capsaicin on the vascular permeability and blood flow were studied in the rat oral mucosa at days 2 and 14 after the unilateral transection of the inferior alveolar nerve (IAN). The distribution of nerve fibers displaying substance P (SP) and calcitonin gene-related peptide (CGRP) immunoreactivity (IR) in the mandibular mucosa was also assessed. While the capsaicin-induced augmentation in vascular permeability was about 50% (P less than 0.05) higher on the intact side (at both days 2 and 14) than on the denervated side, no difference in blood flow elevation was seen between the two sides. Transection of IAN caused only a slight reduction in the density of SP- and CGRP-IR fibers in the mucosa. It is concluded that in addition to the IAN fibers the mandibular mucosa examined also seems to be supplied by other sensory fibers. The presence of accessory trigeminal branches was also supported by immunohistochemical studies.

Steroid hormone receptors in dimethylhydrazine-induced rat colonic tumors.

The presence of steroid hormone receptors was investigated in rat colonic tumors, experimentally induced by 1,2-dimethylhydrazine, and in adjacent normal tissues. Estrogen, progesterone, glucocorticoid, and 5-alpha-dihydrotestosterone receptor levels were measured by the dextran charcoal competitive binding assay. Estrogen receptors were present in 25% of tumors, although not in adjacent normal tissue. Higher levels of glucocorticoid binding in tumor versus adjacent normal tissue were demonstrated in 5 out of 8 cases. Progesterone and 5-alpha-dihydrotestosterone levels in tumor versus adjacent normal tissue were not significantly different. The results reflect the possible endocrine dependence of colonic tumors.