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PubMed1991

Evidence that addition of azathioprine improves renal function in cyclosporine-treated patients with allograft dysfunction.

Several approaches have been attempted to manage renal allograft dysfunction in cyclosporine-prednisone (CsA-Pred)-treated patients. Conversion to conventional therapy and perioperative triple drug have been associated with high rates of acute rejection episodes, infections, or neoplasms. We report our experience in delayed addition of azathioprine (1-2 mg/kg/day) to CsA/Pred protocol in three groups of patients. Group I (n = 9) had chronic renal function deterioration due to chronic rejection; group II (n = 10) had repeated or severe acute rejection episodes despite adequate CsA levels; and group III (n = 8) had CsA toxicity despite drug tapering. In group I, serum creatinine (SCr) had risen from 2.2 +/- 0.9 to 2.9 +/- 0.7 mg/dl over the 6 months prior to Aza addition (P less than 0.05), renal function declining at a rate of -0.14 +/- 0.12 Cr-1/year. In the 6-month post-Aza, renal function improved at a rate of 0.06 +/- 0.06 Cr-1/year and during the entire follow-up at a rate of 0.04 +/- 0.12 Cr-1/year (P less than 0.05) with stable CsA levels (288 +/- 167 vs. 251 +/- 172 ng/dl, NS). In group II response was worse, though the rate of declining renal function prior to Aza (-0.10 +/- 0.10 Cr-1/year) was almost stopped after Aza. In group III there was very good response to Aza addition, as 7 out of 8 patients improved graft function (baseline SCr 2.5 +/- 0.7 mg/dl vs. 1.9 +/- 0.6 mg/dl at last follow-up, P less than 0.05), with significantly decreased CsA levels (480 +/- 97 vs. 268 +/- 120, P less than 0.05). One patient from group II died from pneumonia, and 6 patients (1 from group I and 5 from group II) lost their grafts. Fifteen patients improved graft function, and 9 worsened after addition of Aza. The bad-responders had significantly higher SCr at baseline compared with the good-responders (3.8 +/- 1.8 vs. 2.7 +/- 0.6 mg/dl, P less than 0.01). Amelioration of chronic graft dysfunction can be achieved by delayed addition of Aza to CsA-Pred in patients with chronic rejection or CsA toxicity. This is accompanied by low rate of acute rejection, good patient and graft survival, and low rate of infections. A worse outcome can be seen in patients with high-baseline SCr levels, suggesting the need for addition of Aza in the initial chronic graft dysfunction.

Azathioprine↗
PubMed2001

The impact of long-term nitrogen addition on microbial community composition in three Hawaiian forest soils.

We evaluated the microbial communities in three Hawaiian forest soils along a natural fertility gradient and compared their distinct responses to long-term nitrogen (N) additions. The sites studied have the same elevation, climate, and dominant vegetation, but vary in age of development, and thus in soil nutrient availability and nutrient limitation to plant growth. Fertilized plots at each site have received 100 kg ha year(-1) N addition for at least 8 years. Soil parameters, water content, pH, and ammonium and nitrate availability differed by site, but not between control and N-addition treatments within a site at the time of sampling. Microbial biomass also varied by site, but was not affected by N addition. In contrast, microbial community composition (measured by phospholipid analysis) varied among sites and between control and N-addition plots within a site. These data suggest that microbial community composition responds to N addition even when plant net primary productivity is limited by nutrients other than N. This may have implications for the behavior of forests impacted by atmospheric N deposition that are considered to be "nitrogen saturated," yet still retain N in the soil.

Bacteria↗
PubMed2001

A complete set of maize individual chromosome additions to the oat genome.

All 10 chromosomes of maize (Zea mays, 2n = 2x = 20) were recovered as single additions to the haploid complement of oat (Avena sativa, 2n = 6x = 42) among F(1) plants generated from crosses involving three different lines of maize to eight different lines of oat. In vitro rescue culture of more than 4,300 immature F(1) embryos resulted in a germination frequency of 11% with recovery of 379 F(1) plantlets (8.7%) of moderately vigorous growth. Some F(1) plants were sectored with distinct chromosome constitutions among tillers of the same plant and also between root and shoot cells. Meiotic restitution facilitated development of un-reduced gametes in the F(1). Self-pollination of these partially fertile F(1) plants resulted in disomic additions (2n = 6x + 2 = 44) for maize chromosomes 1, 2, 3, 4, 6, 7, and 9. Maize chromosome 8 was recovered as a monosomic addition (2n = 6x + 1 = 43). Monosomic additions for maize chromosomes 5 and 10 to a haploid complement of oat (n = 3x + 1 = 22) were recovered several times among the F(1) plants. Although partially fertile, these chromosome 5 and 10 addition plants have not yet transmitted the added maize chromosome to F(2) offspring. We discuss the development and general utility of this set of oat-maize addition lines as a novel tool for maize genomics and genetics.

Avena↗
PubMed1987

Improved in vivo and in vitro viability of platelet concentrates stored for seven days in a platelet additive solution.

An additive solution has been developed for storage of platelet concentrates (PC) which sustains improved in vivo and in vitro viability after 7 d of storage in second generation oxygen permeable containers. This platelet additive solution is a protein-free physiologic salt solution fortified with citrate, bicarbonate and glucose. The in vivo quality of the PC was evaluated by autologous radiolabelling with Indium-111-oxine to measure recovery and survival by multiple hit analysis. The in vitro quality was evaluated by total ATP content, hypotonic shock response and extent of shape change with ADP. Ten paired studies were performed with PC from the same donor being stored for 7 d at 22 degrees C in both CPDA-1 plasma and the additive solution. Mean recoveries and survivals were found to be substantially higher with PC stored in the additive solution than with PC stored in CPDA-1 plasma (51.0 +/- 7.8% and 144.1 +/- 15.9 h versus 36.6 +/- 10.7% and 110.4 +/- 31.6 h). The differences were statistically significant (P less than 0.001). The results of the in vitro assays described above parallelled the in vivo results, with statistically significantly superior results (P less than 0.01) for all parameters of PC stored in the additive solution. This study is the first to show that PC quality may be improved and storage extended using an additive solution.

Adenine↗
PubMed1994

Characterization of endothelin (ET) receptors in the isolated gall bladder of the guinea-pig: evidence for an additional ET receptor subtype.

1. We have characterized the receptors mediating contractions induced by endothelin-1 (ET-1), ET-2, ET-3 and the ETB-selective receptor agonists, sarafotoxin 6c (SX6c), IRL 1620, BQ-3020, [Ala1,3,11,15]ET-1 and ET (16-21) in strips of the isolated gall bladder of the guinea-pig (GPGB). We used as antagonists BQ-123 (ETA receptor selective) and PD 145065 (ETA/ETB receptor non-selective). 2. ET-1, ET-2 and ET-3 (10(-10) M to 3 x 10(-7) M) caused similar slowly-developing concentration-dependent contractions of the GPGB. Contractile effects induced by ET-1, ET-2 or ET-3 (at 3 x 10(-7) M) were also similar (230 +/- 25, 241 +/- 7 and 287 +/- 37% of that to histamine at 5 x 10(-6) M, n = 7, 6, 12, respectively). However, the threshold concentration for ET-1 or ET-2 was 10(-10) M whereas it was 3 x 10(-9) M for ET-3. 3. SX6c (10(-10) M to 3 x 10(-7) M) also caused slowly-developing concentration-dependent contractions at a threshold concentration of 10(-10) M (n = 16). However, the contraction caused by SX6c at 3 x 10(-7) M was 116 +/- 9% of that to histamine at 5 x 10(-6) M, which was half of that induced by the same concentration of the ET isopeptides. The contraction induced by IRL 1620 at 3 x 10-7 M (n = 9) was 43 +/- 9% of that to histamine at 5 x 10-6 M, which was one fifth of that produced by the same concentration of ET-1. Contractions induced by BQ-3020 or [Ala1,3,11,15]ET-I at 3 x 10-7 M were even less than those produced by IRL 1620. ET (16-21) was inactive up to 10-5 M. Addition of a concentration of 3 x 10-7 M of ET-1 to tissues with developed contractions induced by the bolus addition of 3 x 10-7 M SX6c caused a further contraction of the GPGB to the level observed with ET-1 alone at 3 x 10-7M (n = 8).4. BQ-123 (10-5 M) did not affect the concentration-response curve to ET-1 and the contraction induced by 3 x 10- M was also not affected (n = 5; 239 +/- 19% of histamine at 5 x 10-6 M). PD 145065(10-5 M) shifted the ET-1 concentration-response curve to the right and the contraction induced by ET-1at 3 x 10-7 M was inhibited by 15% (n = 6; NS). A higher concentration of BQ-123 (10-4 M) caused a significant shift to the right of the ET-1 concentration-response curve similar to that caused by PD 145065 (10-s M) and caused a 24% (n = 6; NS) inhibition of the contractions induced by ET-1 at 3 x 10-7 M. PD 145065 (10-4 M) abolished contractions induced by ET-1 (up to 10- M) and inhibited the response to ET-1 at 3 x 10-7 M by 52% (n = 4; P< 0.05).5. Contractions induced by ET-3 were more sensitive to inhibition by the antagonists. BQ-123 (10-6,10-5 or 10-4 M) inhibited responses to 3 x 10-7 M ET-3 by 66, 71 and 83%, respectively (n = 5, 5, 3;P< 0.05). PD 145065 (10-6, 10-5 or 10-4 M) attenuated more strongly than did BQ-123 the contractions induced by ET-3. For instance, the contractions caused by ET-3 at 3 x 10-7 M were decreased by 73 and 80% (n = 5, 5; P<0.05) in the presence of PD 145065 (10-6 or 10-5 M, respectively). PD 145065(10-4 M) completely abolished contractions to ET-3 (n = 4; up to 3 x 10-7M).6. Contractions induced by SX6c, especially those observed at concentrations lower than 10-8 M, were attenuated by BQ-123 (up to 10-4 M). PD 145065 (10-5M) shifted to the right the concentration response curve to SX6c and inhibited by 38% (P<0.05) the contractions induced by 3 x 10-7M.However, the contractions induced by a bolus addition of a high concentration of SX6c (3 x 10-7 M)and the subsequent addition of an identical concentration of ET-1 on top of SX6c were not affected byBQ-123 (10-6 or 10-5 M).7. These results suggest that ETB receptors are involved in the contractions induced by endothelins in the GPGB. However, SX6c and other selective ETB agonists produced only half or less than half of the contractile response induced by non-selective agonists. In addition, the responses to ET-1 but not to ET-3, were insensitive to the antagonist action of BQ-123 at 10-5 M whereas BQ-123 or PD 145065 at 10-5 M strongly antagonized contractions induced by ET-3. Finally, BQ-123 at 10-4 M inhibited contractions to ET-1 and SX6c. Thus, within the GPGB there may well be additional ET receptor(s) not conforming to the established ETA/ETB receptor subtype classification, as well as ETB receptors.

Amino Acid Sequence↗
PubMed2005

Incidence of complications in patients with implantable cardioverter/defibrillator who receive additional transvenous pace/sense leads.

BACKGROUND: Implantation of an additional pace/sense (P/S) lead is commonly used in patients with implantable cardioverter/defibrillators (ICDs) to overcome P/S defects of integrated defibrillation leads (HV-P/S leads). No information is available about the clinical outcome and the incidence of complications in these patients. METHODS: Retrospective analysis was performed in 151 patients (125 male, age 54.9 +/- 13.6 years, LVEF 48.1 +/- 17.8%, CAD in 86 [57%], DCM in 24 [16%], ARVCM in 11 [7%]) who received an additional P/S lead between 1990 and 2002 (54 patients with abdominal and 97 patients with pectoral ICD system). Statistical analysis was done using Kaplan-Meier survival curves. RESULTS: The average follow-up (FU) after implantation of the additional P/S lead was 43 +/- 27 months. In total 117 patients [77.5%] remain implanted; 22 patients died due to cardiac-related reasons. After a FU of 23 +/- 23 months, 43 patients [28.5%] experienced lead-related problems after implantation of the additional P/S lead: oversensing in 23 [53.5%], insulation defect in 3 [7.0%], fracture in 1 [2.3%], system infection in 4 [9.3%], and defect of the HV-P/S lead in 6 [14.0%] patients. The event-free cumulative survival of the additional P/S lead after 1, 2, and 5 years was 87.0%, 79.8%, and 59.4%, respectively (for pectoral leads: 89.6%, 82.0%, and 60.0%, respectively). CONCLUSIONS: Implantation of an additional P/S lead in case of failure of an HV-P/S lead is safe. However, it is associated with a substantial rate of complications during FU. Therefore, extraction of damaged defibrillation leads instead of implantation of P/S leads should be favored.

Aged↗
PubMed1994

Intracellular pH responses of hybridoma and yeast to substrate addition and acid challenge.

The pHi responses of hybridoma and yeast cells to substrate and external acid additions were measured using the fluorescent pHi indicator, 9-aminoacridine. The pHi change, following CCCP addition, indicated by 9AA, compared very well with that indicated by BCECF. No change in pHi was observed following glucose or glutamine additions to hybridoma cells under glucose- and glutamine-absent conditions. Also, no change in pHi was observed when glucose was added in the presence of low glutamine and when glutamine was added in the presence of low glucose. However, in the presence of amiloride, the pHi of hybridoma cells decreased following glucose addition. Intracellular pH responses of hybridoma and yeast cells to decreases in external pH, effected by acid addition, were dependent on the cellular energy state and acid type. Cells controlled their pHi more tightly under energy-poor conditions compared to energy-rich conditions, and sulfuric acid (strong acid) caused larger changes in pHi compared to pyruvic acid (weak acid). In response to acid addition under energy-rich conditions, the magnitudes of pHi increases in hybridoma were smaller in the presence of amiloride compared to that in the absence of amiloride. Further, pHi responses to a decrease in external pH were slower at submetabolic temperatures.

Acids↗
PubMed1993

Two experiments on the temporal boundaries for the nonlinear additivity of masking.

The present paper describes the results from two experiments which explored the temporal boundary between overlapping and nonoverlapping maskers and its effects on the additivity of masking. In the first experiment, detection thresholds for a short-duration 1000-Hz signal were measured in the presence of two equal-duration broadband maskers which varied in degree of temporal overlap. Following complete overlap of maskers, the temporal separation of masker onsets was systematically varied to create conditions ranging from partially overlapping simultaneous masking to combined forward and backward masking. The signal was always temporally centered between the onset of the first masker and the offset of the second masker. Nonlinear additivity of masking occurred for the majority of subjects when maskers and signal did not overlap, whereas linear additivity resulted for all subjects when the maskers and signal overlapped. In the second experiment, two separate forward maskers were used so that masker/masker overlap could be manipulated independent from masker/signal overlap. Maskers were changed gradually from temporally overlapping, or concurrent, forward maskers to sequential forward maskers. Results for all subjects showed nonlinear additivity for all combined-masker conditions. Together, these two experiments indicated that nonlinear masking additivity is observed when the signal does not overlap temporally with the maskers. However, when maskers and signal overlap temporally (and spectrally), linear additivity is observed.

Acoustic Impedance Tests↗
PubMed1997

Anaerobic activation of toluene and o-xylene by addition to fumarate in denitrifying strain T.

Anaerobic assays conducted with strain T, a denitrifying bacterium capable of mineralizing toluene to carbon dioxide, demonstrated that toluene-grown, permeabilized cells catalyzed the addition of toluene to fumarate to form benzylsuccinate. This reaction was not dependent on the presence of coenzyme A (CoA) or ATP. In the presence of CoA, formation of E-phenylitaconate from benzylsuccinate was also observed. Kinetic studies demonstrated that the specific rate of benzylsuccinate formation from toluene and fumarate in assays with permeabilized cells was >30% of the specific rate of toluene consumption in whole-cell suspensions with nitrate; this observation suggests that benzylsuccinate formation may be the first reaction in anaerobic toluene degradation by strain T. Use of deuterium-labeled toluene and gas chromatography-mass spectrometry indicated that the H atom abstracted from the toluene methyl group during addition to fumarate was retained in the succinyl moiety of benzylsuccinate. In this study, no evidence was found to support previously proposed reactions of toluene with acetyl-CoA or succinyl-CoA. Toluene-grown, permeabilized cells of strain T also catalyzed the addition of o-xylene to fumarate to form (2-methylbenzyl)succinate. o-Xylene is not a growth substrate for strain T, and its transformation was probably cometabolic. With the exception of specific reaction rates, the observed characteristics of the toluene-fumarate addition reaction (i.e., retention of a methyl H atom and independence from CoA and ATP) also apply to the o-xylene-fumarate addition reaction. Thus, addition to fumarate may be a biochemical strategy to anaerobically activate a range of methylbenzenes.

Anaerobiosis↗
PubMed2000

Uridylate addition and RNA ligation contribute to the specificity of kinetoplastid insertion RNA editing.

RNA editing in Trypanosoma brucei inserts and deletes uridylates (U's) in mitochondrial pre-mRNAs under the direction of guide RNAs (gRNAs). We report here the development of a novel in vitro precleaved editing assay and its use to study the gRNA specificity of the U addition and RNA ligation steps in insertion RNA editing. The 5' fragment of substrate RNA accumulated with the number of added U's specified by gRNA, and U addition products with more than the specified number of U's were rare. U addition up to the number specified occurred in the absence of ligation, but accumulation of U addition products was slowed. The 5' fragments with the correct number of added U's were preferentially ligated, apparently by adenylylated RNA ligase since exogenously added ATP was not required and since ligation was eliminated by treatment with pyrophosphate. gRNA-specified U addition was apparent in the absence of ligation when the pre-mRNA immediately upstream of the editing site was single stranded and more so when it was base paired with gRNA. These results suggest that both the U addition and RNA ligation steps contributed to the precision of RNA editing.

Animals↗
PubMed2006

Additional causes for distal sensory polyneuropathy in diabetic patients.

OBJECTIVE: To assess the frequency of additional causes of distal sensory polyneuropathy (DSP) in patients with diabetes mellitus (DM). METHODS: Retrospective review of patients with DM and DSP during a 5 year period. A quantitative sensory score (QSS) was determined at the initial evaluation and extensive laboratory and EMG studies were performed. Patients with one or more potential causes for DSP were compared to those with DM alone. RESULTS: Fifty five patients (53%) had potential additional causes for DSP. These included: neurotoxic medications (seven), alcohol abuse (six), and B12 deficiency and renal disease (four each). The most common laboratory abnormalities were: abnormally low levels of vitamin B6 (11) or B1 (10), monoclonal gammopathy (eight), and hypertriglyceridaemia (eight). Twenty six (25%) subjects had more than one additional cause. Nine (9%) had three or more demyelinating features on EMG. There was a trend toward a lower QSS score (p = 0.05) and reduced mean amplitude of the sensory potentials in those with additional causes. Those with additional causes more often had upper limb sensory symptoms (p = 0.001) and sensory findings (p = 0.003). CONCLUSION: There was a high frequency of additional sources of DSP in patients with DM. These patients more often had sensory symptoms and findings in the hands. Tests that may be useful in the evaluation of DSP in diabetic patients include measures of vitamins B1, B6, B12, serum triglycerides, and immunofixation.

Adult↗
PubMed2003

"Keep a low profile": pesticide residue, additives, and freon use in Australian tobacco manufacturing.

OBJECTIVES: To review the Australian tobacco industry's knowledge of pesticide residue on Australian tobacco and its policies and practices on resisting calls by tobacco control advocates that consumers should be informed about pesticide residue as well as additives. METHODS: Review of previously internal industry documents relevant to pesticides and additives in Australian tobacco located from the Master Settlement Agreement websites. RESULTS: Between 1972 and 1994 Philip Morris Australia was aware that its leaf samples were often contaminated with pesticide residue, sometimes including organochlorine levels described by PM's European laboratories as being "extremely high". Consumers were not advised of the contamination nor products withdrawn. From 1981, the industry also resisted calls to declare fully the extent of use and long term safety data on all additives used in their products. They developed standard public responses that were evasive and misleading and, in 2000, implemented voluntary additive disclosure which allowed the companies to continue to avoid disclosure of any ingredient they deemed to be a trade secret. There was extensive use of ozone depleting freon in Australian tobacco manufacturing. Again, the industry kept this information away from consumers. CONCLUSIONS: Australian smokers are unable to make informed decisions about smoking because pesticide and additive disclosure remains voluntary. The Australian government should regulate tobacco to require full disclosure including information on the likely health consequences of inhaling pesticide and additive pyrolysis products.

Australia↗
PubMed2000

How cigarette additives are used to mask environmental tobacco smoke.

OBJECTIVE: To understand the tobacco industry's research on and use of cigarette additives that alter the perception of exposure to environmental tobacco smoke (ETS). DATA SOURCES: Internal documents from four websites maintained by the major US tobacco manufacturers and company patents pertaining to the use of ETS altering additives obtained from the US Patent and Trademark Office online database. STUDY SELECTION: Electronic searches of the four industry websites and the US patent database were conducted using keywords to identify relevant data. DATA EXTRACTION: Industry documents and patents obtained using an exploratory snowball sampling method were reviewed and grouped into four general categories according to whether the additive(s) described affected ETS visibility, odour, irritation, or emissions. Accuracy of isolated findings was validated through cross comparison of the data sources. DATA SYNTHESIS: Results of this preliminary study provide evidence that tobacco manufacturers have conducted extensive research on the use of chemical additives to reduce, mask, or otherwise alter the visibility, odour, irritation, or emission of ETS. CONCLUSIONS: Findings suggest that the tobacco industry uses additives to reduce the perception of ETS. To protect the public, appropriate regulation of tobacco additives should be mandated.

Humans↗
PubMed1999

Genomic in situ hybridization analysis of Thinopyrum chromatin in a wheat-Th. intermedium partial amphiploid and six derived chromosome addition lines

The genomic origin of alien chromosomes present in a wheat-Thinopyrum intermedium partial amphiploid TAF46 (2n = 8x = 56) and six derived chromosome addition lines were analyzed by genomic in situ hybridization (GISH) using S genomic DNA from Pseudoroegneria strigosa (2n = 2x = 14, SS) as a probe. The GISH analysis clearly showed that the chromosome complement of the partial amphiploid TAF46 consists of an entire wheat genome plus one synthetic genome consisting of a mixture of six S genome chromosomes and eight J (=E) genome chromosomes derived from Th. intermedium (2n = 6x = 42, JJJ(s)J(s)SS). There were no Js genome chromosomes present in TAF46. The J genome chromosomes present in TAF46 displayed a unique GISH hybridization pattern with the S genomic DNA probe, in which S genome DNA strongly hybridized at the terminal regions and weakly hybridized over the remaining parts of the chromosomes. This provides a diagnostic marker for distinguishing J genome chromosomes from Js or S genome or wheat ABD genome chromosomes. The genomic origin of the alien chromosomes present in the six derived chromosome addition lines were identified by their characteristic GISH hybridization patterns with S genomic DNA probe. GISH analysis showed that addition lines L1, L2, L3, and L5 carried one pair of J genome chromosomes, while addition lines L4 and L7 each carried one pair of S genome chromosomes. GISH patterns detected by the S genome probe on addition line of L1 were identical to those of the J genome chromosomes present in the partial amphiploid TAF46, suggesting that these chromosomes were not structurally altered when they were transferred from TAF46 to addition lines.

Journal Article↗
PubMed1990

Application of the isobologram technique for the analysis of combined effects with respect to additivity as well as independence.

Combined actions of two substances with similar effects are frequently expressed by pairs of doses that produce a fixed response, usually 50%, in so-called isobolograms (ED50 isobolograms). In addition to the dose scales in such graphs we propose the addition of effect scales, where possible, to indicate the effect at certain doses, e.g., the ED30. We further propose to construct isoboles for expected independent interaction, in addition to the additivity line, for which purpose a simple procedure is delineated. In practice, an independent isobole for 50% effect passes through the point formed by the ED30s of A and of B in ED50 isobolograms. Thus, the ED30s constitute the "zenith" of an independent isobole in ED50 isobolograms. It is shown that theoretical independent isoboles can either represent additive, overadditive, or underadditive interactions, depending on the steepness of the dose-response curves of the components. Hence, drugs with shallow dose-response curves exhibit overadditive independent effects, compounds with exponentially steep curves show additive independent interactions. Substances with very steep dose-response curves, producing lethal effects, exhibited marked underadditive effects which could be ascribed largely to an independent mechanism of action of the components. Hence, the inclusion of independent isoboles into conventional isobolograms provides new insights into the mechanisms of interactions and into the actions of the components. Interactions can thus be characterized better and more completely, and misinterpretations appear less likely than with conventional isoboles.

Animals↗
PubMed2005

Family burden during exacerbation of schizophrenia: quantification and determinants of additional costs.

BACKGROUND/AIMS: Family members of people with schizophrenia are heavily burdened. Thus, we aimed at quantifying the amount of additional efforts during the two weeks before hospitalisation of acute exacerbating psychosis compared to the time before. METHODS: By means of the semi-structured 'Interview for Measuring the Burden on the Family' we interviewed relatives of people with schizophrenia. To quantify additional burden we asked how much time a person who would take over the additional burden has to afford. Subscales of different sources of burden and total scales were correlated. RESULTS: An additional 8.9 hours per day would have to be spent in favour of the patient, which results in additional costs of Euro 3,115-Euro 4,984 (ca. pounds 2,100-3,400) for two weeks. The main sources of additional burden are quantity, quality and nature of contacts to the affected. This includes the frequency of contact to the affected, the whereabouts and symptoms of the affected, as well as the social contacts of the relatives. CONCLUSIONS: Our results clarify the quantitative aspect of care provided by relatives of people with schizophrenia. Apart from the practical and emotional help to relatives the development of a diversified network of community psychiatry services, e.g. day and night hospitals, as well as crisis accommodations should be established.

Acute Disease↗
PubMed2001

Extrusion/spheronization of pectin-based formulations. II. Effect of additive concentration in the granulation liquid.

PURPOSE: The aim of this study was to improve the formation of spherical pectin pellets by investigating the effect of additive concentration in the granulation liquid on the shape and size of the products as well as by identifying an optimal additive concentration. METHODS: High-methoxylated, low-methoxylated, and amidated low-methoxylated pectin types were evaluated in combination with different concentrations of methanol, ethanol, citric acid, lactic acid, and calcium chloride. Pellets were prepared in a power-consumption-controlled twin-screw extruder, then spheronized and dried. The moisture content of the extrudate was determined, and the final products were characterized by image analysis and sieving analysis. A cloud point test was employed for the identification of an optimal additive concentration. RESULTS: The concentration of additive in the granulation liquid affected the moisture content of the extrudate and the shape, size, and mechanical stability of the pectin pellets. Improvements in the pellet characteristics are dependent on the pectin type employed. The 2 low-methoxylated pectins were more sensitive to concentration changes than was the high-methoxylated type. Above a certain threshold concentration, the quality of the pellets are improved. This additive concentration differs according to type of pectin and type of additive. CONCLUSION: It was demonstrated that there is a concentration-dependent interaction between pectin and substances added to the granulation liquid that can be utilized to improve the formation of spherical pectin pellets.

Calcium Chloride↗
PubMed1998

Addition of catfish gonadotropin-releasing hormone (GnRH) receptor intracellular carboxyl-terminal tail to rat GnRH receptor alters receptor expression and regulation.

Mammalian GnRH receptor (GnRHR) is unique among G protein-coupled seven-transmembrane segment receptors due to the absence of an intracellular C-terminal tail frequently important for internalization and/or desensitization of other G protein-coupled receptors. The recent cloning of nonmammalian (i.e. catfish, goldfish, frog, and chicken) GnRHRs shows that these contain an intracellular C terminus. Addition of the 51-amino acid intracellular C terminus from catfish GnRHR (cfGnRHR) to rat GnRHR (rGnRHR) did not affect rGnRHR binding affinity but elevated receptor expression by about 5-fold. Truncation of the added C terminus impaired the elevated receptor-binding sites by 3- to 8-fold, depending on the truncation site. In addition, introducing the C terminus to rGnRHR altered the pattern of receptor regulation from biphasic down-regulation and recovery to monophasic down-regulation. The extent of down-regulation was also enhanced. The alteration in receptor regulation due to the addition of a C terminus was reversed by truncation of the added C terminus. Furthermore, addition of the cfGnRHR C terminus to rGnRHR significantly augmented the inositol phospholipid (IP) response of transfected cells to Buserelin, but this did not result from the elevation of receptor-binding sites. Addition of the C terminus did not affect Buserelin-stimulated cAMP and PRL release. GH3 cells transfected with wild-type cfGnRHR did not show measurable Buserelin binding or significant stimulation of IP, cAMP, or PRL in response to Buserelin (10[-13]-10[-9] M). GH3 cells transfected with C terminus-truncated cfGnRHR showed no IP response to Buserelin (10[-13]-10[-7] M). These results suggest that addition of the cfGnRHR intracellular C terminus to rGnRHR has a significant impact on rGnRHR expression and regulation and efficiency of differential receptor coupling to G proteins.

Amino Acid Sequence↗