[Some indices of water-salt homeostasis development in neonates who sustained various forms of hypoxia].
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Female↗
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[Surgical treatment for subacute left ventricular free wall rupture complicating acute myocardial infarction--pericardial patch gluing method].
We reviewed 22 cases with surgical repair for subacute left ventricular free wall rupture complicating acute myocardial infarction. Different operative technique was used. Direct closure or patch repair with infarctectomy was preformed in first patients with a great difficulty in hemostasis. Since 1988 we sutured a large pericardial patch covering the infarcted myocardium under extra corporeal circulation in 11 patients (pericardial patch suture technique). From 1993 we began to glue a pericardial patch with Aron alpha without cardiopulmonary bypass (pericardial patch gluing technique). There were eight early death and four late death. Most common cause of death was low cardiac output syndrome (LOS). With medical therapy 13 patients in cardiogenic shock improved before surgery and only three developed postoperative LOS, but all six patients with sustained shock developed LOS without survivor (p = 0.007). Two of the five patients underwent direct closure or infarctectomy and seven of the 11 employed pericardial patch suture technique developed LOS, but none of the six used pericardial patch gluing technique developed LOS. Medical treatment such as intraaortic balloon pumping, catecholamine and subxyphoid drainage in order to improve hemodynamic condition before surgery is extremely important. Pericardial patch gluing technique seems to be useful since cardiac function would be maximally preserved.
Aged↗
Development of self-sustaining limbic status epilepticus by continuous ventral hippocampal stimulation followed by low dose pilocarpine in rats.
Sequential treatment of rats with low doses of lithium and pilocarpine, a high dose of pilocarpine, or continuous hippocampal stimulation [CHS] (9 epochs, 10 min each) is reported to result in status epilepticus (SE). We report a novel method to establish SE based on continuous ventral hippocampal stimulation (5 epochs) followed by low dose pilocarpine (40 mg/kg) challenge. Motor limbic seizures occured in all the control rats. The latency to spike activity was 15 +/- 1 min after pilocarpine administration. Ventral hippocampal [VHc] and cortical EEG recordings were used to monitor the protective effect of diazepam (5 mg/kg). Except phenobarbital, all the three drugs completely prevented all the phases of seizure activity. Initiation of spikes was significantly prolonged by phenobarbital pretreatment. Further study on the characteristics of these convulsions offers a unique possibility for the recognition of brain regions, pathways, and neurotransmitters engaged in the spread of seizures in this model.
Animals↗
[Injection molding of preoral sustained-release preparations. 5. Development of a solid foam body].
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Chemistry, Pharmaceutical↗
Development of cholinergic and inhibitory non-adrenergic non-cholinergic responses in the rat gastric funds.
1. Cholinergic contractions and inhibitory non-adrenergic non-cholinergic (NANC) relaxations were studied in longitudinal muscle strips of the gastric funds of 2, 4 and 8 week old rats. 2. Contractions induced by electrical stimulation of the cholinergic neurones and by administration of acetylcholine decreased during development. The potentiating effect of physostigmine was similar in the 3 age groups. 3. Short train stimulation in NANC conditions induced fast relaxations, which were more pronounced in 4 and 8 week than in 2 week old rats. These relaxations were almost completely inhibited by NG-nitro-L-arginine methyl ester (L-NAME) in the 3 age groups. The nitric oxide-induced relaxations did not change during development. 4. Sustained electrical stimulation in NANC conditions induced an initial relaxation, which was almost totally blocked by L-NAME, followed by an almost complete recovery of tone at lower frequencies of stimulation. At higher frequencies of stimulation, the recovery of tone was incomplete or absent. This sustained relaxation was only partially reduced by L-NAME and almost abolished by L-NAME plus alpha-chymotrypsin. The initial relaxations increased during development, while the sustained relaxations remained similar during this period. Vasoactive intestinal polypeptide-induced relaxations were also similar in the 3 age groups. 5. These results show that the sensitivity of the gastric fundus to acetylcholine decreases from 2 weeks to 8 weeks postnatally, while the importance of the nitrergic innervation increases during this period.
Acetylcholine↗
HPLC determination and pharmacokinetics of sustained-release bupropion tablets in dogs.
The pharmacokinetics and bioequivalency of a newly developed sustained-release bupropion tablet was studied in six dogs after single oral administration and compared with a regular tablet (RT) in randomized two-period crossover design. A sensitive and rapid HPLC method was developed and validated for the quantitative determination of bupropion in dog plasma. The compound and the internal standard (I.S.) (hydroxyethylfludiazepam) were extracted from the plasma samples by liquid-liquid extraction. The extracts were analyzed by a reversed-phase HPLC with 50 mmol/l phosphate buffer (pH 5.5)-methanol (45:55, v/v) as the eluent. The assay was specific for bupropion. The calibration curves were linear in the range between 1 and 750 ng/ml. The validated lower limit of quantification was 1 ng/ml. The overall precision (expressed as R.S.D.) of quality controls were within 15%. The method was successfully applied to the bioequivalency study of bupropion in the two formulations. The Cmax of sustained-release tablet (ST) was significantly lower than that of the RT and the Tmax was significantly longer than that of the RT (P<0.05). The relative bioavailability of the ST was (99.1+/-1.51)%, the results of ANOVA and two one sided tests indicated that the new ST exhibited good sustained release properties and was bioequivalent to the RT.
Animals↗
Galenic development and pharmacokinetic profile of indapamide sustained release 1.5 mg.
In accordance with international guidelines recommending the use of low doses of antihypertensive agents, a new formulation of indapamide--indapamide sustained release (SR)--has been developed. Indapamide has been used worldwide for many years as an immediate release (IR) formulation at a dose of 2.5 mg. The IR formulation leads to plasma peaks of indapamide immediately after administration of the tablet. These peaks are responsible for possible unfavourable electrolyte or metabolic effects relating to indapamide blood concentrations. The SR formulation, by eliminating plasma peaks, allows a smoothing of the pharmacokinetic profile of indapamide. This new galenic formulation is based on a hydrophilic matrix tablet composed of a cellulose derivative, methylhydroxypropylcellulose (MHPC), and a binder, polyvinylpyrrolidone (povidone). The originality of the matrix lies in the percentages of MHPC and povidone, which permit a linear release in vitro of indapamide. After optimisation, the chosen ratio of these 2 constituents allowed the release of more than 70% of the dosage over 16 hours in a very reproducible manner. The 2 tested formulations (SR and IR) have the same bioavailability; however, the main pharmacokinetic parameters of the new SR 1.5 mg formulation, calculated after single and repeated administration, show a profile typical of an SR formulation, i.e. a lower maximum concentration (Cmax), a longer time to Cmax, and the same minimum concentration as the IR formulation. This new SR formulation, which allows a reduction in the daily dose of indapamide from 2.5 to 1.5 mg, leads to an improvement in its efficacy/tolerability ratio, thereby meeting the recommendations of the international guidelines for the treatment of essential hypertension.
Biological Availability↗
Development of implant tablet for a week-long sustained release.
An implant tablet for a week-long sustained release was developed by the direct compression method using poly-DL-lactic acid (PLA) and poly(DL-lactic acid-co-glycolic acid) copolymer (PLGA) as a matrix and phenol red (PR) as a model drug. The in vitro release was affected by formulations, especially by drug content and polymer species. The release rate correlated with the rate of absorption of water. The implant tablet (30 mg) containing 1 mg of PR, prepared using PLGA (MW 10,000; lactic acid/glycolic acid=1:1, mol/mol) by compression at 50 kg/cm(2) for 10 s, was found to efficiently exhibit a week-long sustained release in vitro, and applied in vivo. The remaining amount or plasma concentration of PR after s.c. administration of the implant tablet to rats demonstrated that the implant tablet showed a week-long sustained release in vivo. The present implant tablet is suggested to be useful as a drug delivery system for supplying drugs for approximately 1 week.
Animals↗
Measurement of visual sustained attention in schizophrenia using signal detection analysis and a newly developed computerized CPT task.
Sustained attention in schizophrenia was assessed with a newly developed, computer-controlled, modified version of the continuous performance test in which specific attentional effects can be empirically distinguished from nonspecific factors by signal detection theory (SDT). Results indicated that patients showed a more rapid decline in specific attentional, but not nonspecific processes, as measured by SDT parameters of A' and B", respectively.
Adult↗
Characterization of water adsorption onto carbonaceous materials produced from food wastes.
The recycling of organic wastes has become very important and the development of technology for recycling organic wastes needs to sustain industrial development. In this study, techniques for producing carbonaceous materials from organic wastes are described and water adsorption is characterized. The organic wastes used are coffee grounds and oolong tea leaves carbonized at 673 to 1073 K. The iodine adsorption capacity of the carbonaceous materials increased with increased carbonization temperature. The amount of water adsorbed onto the carbonization materials produced from oolong tea leaves at 873 K for 2 h was the highest. The Freundlich constant 1/n and the differential heat of adsorption of the carbonaceous materials produced from oolong tea leaves were greater than that of the carbonaceous materials produced from coffee grounds. The ability to humidity control can be estimated by the difference between the amount of water adsorbed relative pressure 0.90 and that at relative pressure 0.55. The ability to humidity control was the greatest for the carbonaceous materials produced from the oolong tea leaves at 873 K for 2 h and did not depend upon the adsorption temperature. These results indicated that the carbonaceous materials produced from oolong tea leaves at 873 K for 2 h could have more humidity control.
Adsorption↗
A proposed sustainable BNR plant with the emphasis on recovery of COD and phosphate.
Water problems have to be solved in an integrated way, and sustainability has become a major issue. For this reason, developing more sustainable wastewater treatment processes is needed. New discoveries and good understanding on microbial conversions of nitrogen and phosphorus make more sustainable processes possible. New options for decentralized sustainable sanitation are generally compared to conventional sewage systems, we think that for a proper comparison also innovative centralized treatment schemes should be evaluated. In this article, a more sustainable WWTP is proposed for municipal wastewater treatment, mainly based on the principles of denitrifying dephosphatation and anaerobic ammonium oxidation (ANAMMOX). The proposed system consists of a first stage of the A/B process in which maximal sludge production is achieved. In this way, COD is regained as sludge for methanation. The following BCFS and CANON processes can remove N and P with minimal or no COD need. As a potential fertiliser, struvite can easily be removed from the sludge water by adding magnesium compounds. A case study is done on the basis of the mass balance over the proposed plant. The effluent from the system has a good quality to be recycled. This could also make a contribution to meeting the world's water needs and lessening the impact on the world's water environment. Since all the separate units are already applied or tested on pilot-scale, no problems for technical implementation are foreseen.
Bacteria, Anaerobic↗
Phorbol ester (PMA)-induced biphasic contraction of the rat aorta and effects of sodium nitroprusside and forskolin on the contraction.
Effects of sodium nitroprusside (SNP) and forskolin on the contractile responses of aortic strips to phorbol 12-myristate 13-acetate (PMA) were investigated in the present study. PMA produced biphasic contraction in the rat aorta, i.e. sustained, slowly developing contraction followed by phasic contraction superimposed on the sustained contraction. Both sustained contraction and phasic response were completely abolished by treatment with staurosporine. Phasic contraction was completely inhibited by nicardipine or removal of external Ca2+, whereas sustained contraction was not affected by nicardipine. Both SNP and forskolin inhibited sustained contraction. Ca(2+)-induced contraction of the aorta which had been treated with PMA in Ca(2+)-free medium was completely inhibited by nicardipine and was partially inhibited by forskolin, but SNP had no effect on the Ca(2+)-contracture. These results suggest that 1) PMA contacts the rat aorta through stimulation of protein kinase C and activation of voltage-dependent Ca2+ channels; 2) there may be great differences in the effects of cyclic GMP and cyclic AMP on the protein kinase C-induced sustained and phasic contractions.
Adenylyl Cyclases↗
HPLC determination and steady-state bioavailability study of levodropropizine sustained-release tablets in dogs.
A simple HPLC method using UV detection was developed and validated for the determination of levodropropizine (LDP) in dog plasma. The sample was prepared for injection using a liquid-liquid extraction method with 1-phenypiperazine as the internal standard. The mobile phase was methanol-diethylamine solution (0.05 M) (20:80, v/v, pH adjusted to 3.0 with H3PO4) with a detection wavelength of 240 nm. The limit of quantitation (LOQ) of LDP in a biological matrix was determined to be 25.25 ng/mL. The calibration curve was linear across the concentration range of 25.25 to 2020 ng/mL. The intra-day and inter-day precision values (CV %) were within 7% and accuracy (R.E. %) was within 6% of the nominal values for medium (252.5 ng/mL) and high (2020 ng/mL) LDP concentrations. For the LDP concentration at the LOQ, the intra-day and inter-day precision and accuracy were within 20% and 10%, respectively. The average absolute recovery for LDP was 70.28%. This method was successfully used to analyze plasma samples in a steady-state bioavailability study of a newly developed sustained-release LDP tablets (SR) using immediate-release tablets (IR) as the reference. The relative bioavailability of the SR was determined to be 106.3 +/- 12.8% (n=6). The Cmax of the SR was significantly lower (P<0.05), and the tmax was significantly longer than that of the IR (P<0.05). The results of ANOVA and two one-sided tests indicated that the SR exhibited acceptable sustained release properties and was bioequivalent to the IR.
Animals↗
Synchronized and sustained release of multiple components in silymarin from erodible glyceryl monostearate matrix system.
Development of sustained delivery systems for herbal medicines was very difficult because of their complexity in composition. The concept of synchronized release from sustained release systems, which is characterized by release of multiple components in their original ratio that defines a herbal medicine, served as the basis for keeping the original pharmacological activity. In this study, erodible matrix systems based on glyceryl monostearate and polyethylene glycol 6000 or poloxamer 188 were prepared to perform strict control on synchronized release of the five active components of silymarin, i.e. taxifolin, silychrystin, silydianin, isosilybin and silybin. The matrix system was prepared by a melt fusion method. Synchronized release was achieved with high similarity factor f(2) values between each two of the five components. Erosion profiles of the matrix were in good correlation with release profiles of the five components, showing erosion-controlled release mechanisms. Through tuning some of the formulation variables, the system can be adjusted for synchronized and sustained release of silymarin for oral administration. In vitro hemolysis study indicated that the synchronized release samples showed a much better stabilizing effect on erythrocyte membrane.
Animals↗
Multicomposite ultrathin capsules for sustained ocular delivery of ciprofloxacin hydrochloride.
PURPOSE: The present work is intended to develop a sustained bioadhesive drug delivery system for delivery of Ciprofloxacin Hydrochloride in Cul-de-Sac for sustained and effective antimicrobial chemotherapy. For this, ultrathin multicomposite capsular systems were selected. METHODS: Multicomposite ultrathin capsules are molecular assemblies of tailored architecture having layer-by-layer adsorption of oppositely charged macromolecules onto colloidal particles. In the present study colloidal calcium phosphate core and gluateraldehyde fixed RBCs were used as core on which alginate (-vely charged) and polyallylamine hydrochloride (+vely charged) polyelectrolyte coating was deposited alternatively upto 10th layer. The coating in each subsequent layer was determined by changes in zeta potential. Ciprofloxacin hydrochloride was loaded in the capsules by incubation with the capsules suspended in phosphate buffer saline pH 7.4. The cores of the capsules were then removed by treatment with 0.1N HCl for calcium phosphate core and by sodium hypochlorite for RBC cored capsules. The hollow ciprofloxacin HCl loaded capsules were the evaluated in-vitro for pattern of layer-by-layer drug loading, drug release, stability at various temperatures and ionic concentrations and corneal retention. RESULTS: The core removal process was found to have minimal effects on drug loading in capsules. The drug loading was found to be higher for RBC cored hollow capsules and hence release rate was lower as compared to calcium cored hollow capsules. Draize test for corneal irritancy proved that the capsules were not irritating. The capsules were found to deliver the ciprofloxacin in cul-de-sac of rabbit's eyes for prolonged period. CONCLUSION: Based on corneal retention studies and tear drug concentration, the capsules can be considered for suitable and safe use for sustained ocular delivery of drugs.
Adsorption↗
Conservation and development projects in the Brazilian Amazon: lessons from the Community Initiative Program in Rondônia.
Community-based conservation and development has become the prevailing programmatic paradigm of conservation organizations and development donors over the last 20 years, spawning a myriad of integrated conservation and development projects (ICDP) around the world. Appealing for its ambitious aspiration to harmonize sustainable economic development at the local level with the conservation of legally established protected areas (e.g., parks and reserves), the ICDP approach recently has drawn criticism from conservation biologists for failing to ensure adequate protection of biodiversity. Development planners and economists have also raised questions about the financial sustainability of ICDPs in practice and the replicability of the model from highly local contexts to larger regional scales. This paper briefly reviews the central elements of the concept of integrated conservation and development and the emerging debate over its effectiveness. A description of the Community Initiative Program (CIP), a pilot program of the Rondônia Natural Resources Management project (PLANAFLORO) in the western Brazilian Amazon state of Rondônia, follows. The CIP is a significant experiment because it boldly attempted to apply the principles of ICDP to the regional scale involving numerous different communities in one program simultaneously. Based on the author's mid-term review of the CIP in 1999, the development and conservation impacts of the program are considered. While the CIP has not significantly curbed the degradation of protected areas in Rondônia as intended, the evidence suggests lower rates of deforestation in municipios (i.e. counties) with the highest concentrations of CIP projects. Although the economic development impacts are mixed, approximately 50% of the projects delivered tangible benefits to local communities. Lessons learned from the CIP are presented in the final section. Among the lessons learned from the CIP, detailed in the final section, are several that will be familiar to other ICDP evaluators: the importance of thematic coherence in initial project design, the need for explicit attention on environmental conservation objectives, deficient institutional capacity of implementing organizations, inadequate attention to women's concerns and roles in community projects, and lack of technical criteria for measuring project sustainability.
Agriculture↗
Sustained Bmp signaling is essential for cloaca development in zebrafish.
Bone morphogenetic protein (Bmp) signaling has long been known to be important for the early development of the ventral mesoderm, including blood, vasculature and kidney cells. Although Bmp genes are continually expressed in the ventral cells throughout gastrulation and somitogenesis, previous studies in zebrafish have not addressed how the role of Bmp signaling changes over time to regulate ventral mesoderm development. Here, we describe the use of a transgenic inducible dominant-negative Bmp receptor line to examine the temporal roles of Bmp signaling in ventral mesoderm patterning. Surprisingly, we find that Bmp signaling from the mid-gastrula stage through early somitogenesis is important for excluding blood and vascular precursors from the extreme ventral mesoderm, and we show that this domain is normally required for development of the cloaca (the common gut and urogenital opening). Using a novel assay for cloacal function, we find that larvae with reduced mid-gastrula Bmp signaling cannot properly excrete waste. We show that the cloacal defects result from alterations in the morphogenesis of the cloaca and from changes in the expression of genes marking the excretory system. Finally, we show that HrT, a T-box transcription factor, is a Bmp-regulated gene that has an essential function in cloacal development. We conclude that sustained Bmp signaling plays an important role in specification of the zebrafish cloaca by maintaining the fate of extreme ventral cells during the course of gastrulation and early somitogenesis. Furthermore, our data suggest that alterations in Bmp signaling are one possible cause of anorectal malformations during human embryogenesis.
Animals↗
Development of an integrated and sustainable rural service for people with diabetes in the Scottish Highlands.
INTRODUCTION: The number of people with diabetes is increasing leading to a greater burden on health care services. The impact of the growing prevalence is accentuated by remote and rural demographic and geographic characteristics. Highland is a sparsely populated remote and rural area in the north of Scotland, characterised by poor access to health-care services and pockets of marked deprivation. Centralised policy developments demanding local implementation compounded the pressures on a system that already had waiting times of over 90 weeks for some people with diabetes. A regional review of services, engaging stakeholders from all disciplines and geographical locations was required to develop acceptable and sustainable solutions. This article describes the extensive mapping process involved, how solutions were derived, and suggests a new service structure to encompass remote health-care issues. METHODS: Health-care professionals with an interest in diabetes were identified and workshops were organised to include the remote areas of Highland. Patient and carers views were ascertained through workshops and supplemented by written submissions. Using the redesign methodology the patient pathway was mapped, noting service deficiencies and good practice. The information gathered was constructed into a service-level map representing the patient journey. A conference was organised to develop solutions to the issues raised during the mapping process. From these solutions a new service configuration was constructed. RESULTS: Over 300 health-care professionals patients and carers contributed. Fourteen workshops were held across the region including the remote areas, providing 15 local maps of the patient pathways subsequently amalgamated into a service-level map. The current patient pathway in Highland follows a traditional and dichotomous cycle of care in the primary and secondary care setting, partly reflecting the rural nature of healthcare in the Highlands. Four main areas for service improvement were identified: a reduction in waiting times for secondary care out patients; an improvement in communication between health-care professionals; further education for both health-care professionals and patients; and the use and role of allied health professionals. Seventeen solutions were recommended, including the introduction of a managed clinical network, use of an integrated IT system, use of a remote access consultation clinic, and web-based peer education and group sessions for allied health professionals. A new service configuration was proposed with the patient at the centre of a non-hierarchical system using standardised referral letters with a seamless flow of information. CONCLUSION: Local processes for the implementation of government directives are imposing pressures on relatively smaller organisations. These pressures develop as a result of attempts to ensure local ownership and in overcoming the difficulties unique to the remote and rural setting. Further evaluation of the implementation of initiatives to solve the issues of service planning in remote areas is needed to clarify their level of effectiveness.
Diabetes Mellitus↗