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Inhibition of osteoporosis induced by protein deficient (PD) food intake by active vitamin D(3) and vitamin K(2) in rats.

Independent use of K(2) and D(3) and simultaneous application of K(2) and D(3) inhibited the development of osteoporosis caused by PD food intake. The ALP activity of urine as a marker of bone formation osteoporosis did not rise in rats fed PD foods containing D(3), K(2) or both together. Body and womb weights fell in rats fed PD foods with D(3) K(2) and both D(3), K(2). Osteoporosis caused by PD food intake found to be very similar to type II osteoporosis in respects of inhibition by D(3) and K(2) and rising urinary ALP activity.

Alkaline Phosphatase↗

Young women with PD: a group work experience.

Parkinson's Disease (PD) prior to the age of 40 affects between 5-10% of the PD population. The psychosocial changes that patients with early PD encounter, may be more devastating and disabling than the actual motor disability. The paper describes a unique experience in groupwork with young female PD patients treated in the Movement Disorders Unit of the Tel Aviv Sourasky Medical Center. The paper focuses on the special issues which characterized this group's experience: stigma, body and sexual image, and personality traits.

Adaptation, Psychological↗

Secondary structure and Pd(II) coordination in S-layer proteins from Bacillus sphaericus studied by infrared and X-ray absorption spectroscopy.

The S-layer of Bacillus sphaericus strain JG-A12, isolated from a uranium-mining site, exhibits a high metal-binding capacity, indicating that it may provide a protective function by preventing the cellular uptake of heavy metals and radionuclides. This property has allowed the use of this and other S-layers as self-assembling organic templates for the synthesis of nanosized heavy metal cluster arrays. However, little is known about the molecular basis of the metal-protein interactions and their impact on secondary structure. We have studied the secondary structure, protein stability, and Pd((II)) coordination in S-layers from the B. sphaericus strains JG-A12 and NCTC 9602 to elucidate the molecular basis of their biological function and of the metal nanocluster growth. Fourier transform infrared spectroscopy reveals similar secondary structures, containing approximately 35% beta-sheets and little helical structure. pH-induced infrared absorption changes of the side-chain carboxylates evidence a remarkably low pK < 3 in both strains and a structural stabilization when Pd((II)) is bound. The COO(-)-stretching absorptions reveal a predominant Pd((II)) coordination by chelation/bridging by Asp and Glu residues. This agrees with XANES and EXAFS data revealing oxygens as coordinating atoms to Pd((II)). The additional participation of nitrogen is assigned to side chains rather than to the peptide backbone. The topology of nitrogen- and carboxyl-bearing side chains appears to mediate heavy metal binding to the large number of Asp and Glu in both S-layers at particularly low pH as an adaptation to the environment from which the strain JG-A12 has been isolated. These side chains are thus prime targets for the design of engineered S-layer-based nanoclusters.

Bacillus↗

Adsorption behavior of noble metal ions (Au, Ag, Pd) on nanometer-size titanium dioxide with ICP-AES.

The adsorption behavior of gold (Au), silver (Ag) and palladium (Pd) on nanometer-size titanium dioxide (NSTD) at low concentrations was studied using inductively coupled plasma atomic emission spectrometry (ICP-AES). A preconcentration procedure of the analytes was carried out using NSTD as a solid-phase extractant before their determination by ICP-AES. The optimum conditions for adsorption were studied in detail, and under the condition that Au, Ag and Pd ions could be adsorbed and recovered quantitatively. The static adsorption capacities of Au, Ag and Pd on NSTD were 22.63, 14.06 and 11.82 mg/g, respectively. For the elution of gold, silver and palladium, a mixture of 5% thiourea solution and 3 mol L(-1) HNO3 was used. The parameters tested included: pH conditions, contact time of the analytes with NSTD, flow rate, adsorption capacity and sorption kinetics. According to the definition of IUPAC, the detection limits (3sigma) of this method for Au, Ag and Pd with an enrichment factor of 50 were (0.016), (0.006) and (0.012) microg mL(-1), respectively, the relative standard deviations (RSD) were 8.7%, 4.5% and 7.4%, respectively (n = 6). Some geological samples were determined with satisfactory results.

Journal Article↗

No effect of angiotensin II AT(2)-receptor antagonist PD 123319 on cerebral blood flow autoregulation.

Blockade of the renin-angiotensin system with angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin AT1-receptor antagonists shift the limits of autoregulation of cerebral blood flow (CBF) towards lower blood pressure (BP). The role of AT2-receptors in the regulation of the cerebral circulation is uncertain. Hence, the present study investigated the effect on CBF autoregulation of blocking of angiotensin AT2-receptors with PD 123319 in spontaneously hypertensive rats (SHR). Anaesthetised and ventilated SHR were given PD 123319, 0.36 mg/kg/min, intravenously, and compared with a control group. CBF was measured by the intracarotid 133xenon injection method and BP was raised by noradrenaline infusion and lowered by controlled haemorrhage in separate groups of rats. The limits of autoregulation were determined by computed least-sum-of-squares analysis. PD 123319 did not influence baseline CBF, but resulted in a minor BP decrease (10 control and 10 treated rats). The lower limit of CBF autoregulation (eight treated and eight control) as well as the upper limit of CBF autoregulation (eight treated and eight control) were not significantly different in PD 123319 and control animals (lower limit treated 102+/-4 mmHg and control 94+/-4; NS, and upper limit treated 171 +/- 10 mmHg and control 162+/-7; NS). These findings indicate that acute AT2-receptor blockade does not influence CBF autoregularion.

Angiotensin Receptor Antagonists↗

Effects of intravenous PD 123319 on haemodynamic and arterial stiffness indices in healthy volunteers.

Relatively little is known about the functional expression of cardiovascular angiotensin type 2 (AT2)-receptors in healthy young adult humans. We performed a randomised, placebo-controlled crossover study of the effects of intravenous administration of the selective AT2-receptor antagonist PD 123319 on haemodynamics and arterial stiffness in normal volunteers. Sixteen normal subjects aged 29.9+/-13.8 years (range 18-30 years) received an intravenous infusion of PD 123319 (10 mcg/minute for 5 minutes) and placebo, separated by one week. Haemodynamics (cardiac index, stroke index and systemic vascular resistance) were measured non-invasively using a BioZ.com thoracic impedance detection system. Blood pressure was measured from an arm cuff using oscillometry. Stiffness index, a measure of arterial stiffness, was measured using a Pulse Trace recorder. No significant changes in blood pressure (p=0.92), cardiac index (p=0.52), stroke index (p=0.61), systemic vascular resistance index (p=0.32) or stiffness index (p=0.57) was demonstrated following PD 123319 infusion, compared with placebo. The results of this study do not support the functional presence of cardiovascular AT2-receptors that mediate acute haemodynamic effects in healthy young adults. It remains possible that higher doses of PD 123319 may be required to demonstrate functional cardiovascular AT2-receptors in this population, if they are present.

Adolescent↗

Delivering adequacy in PD therapy.

Providing appropriate peritoneal dialysis is an ongoing challenge to renal care providers. As the residual renal function and the peritoneal permeability are likely to change with time, the dose provided by the PD regimen needs to be adjusted. Rather than waiting for clinical signs of underdialysis, the practising nephrologist and the PD nurse today have access to diagnostic tools to assist in the prescription of adequate therapy. Peritoneal dialysis prescription involves setting up a personalized dialysis schedule aimed at obtaining satisfactory clearance and ultrafiltration rates while respecting the patient's life-style as far as possible. The PD nurse has the most patient contact and thus plays a pivotal role with the other healthcare professionals in the care of the patients. As providers, it is our responsibility to inform the patients about their own care. As PD is a method of home dialysis, patients must have self responsiveness, technical and psycho social skills to deal well with the method.

Blood Urea Nitrogen↗

A prospective multicenter comparison of peritonitis in peritoneal dialysis patients aged above and below 65 years. Levante PD Multicenter Group.

Various authors have found peritonitis rates in older peritoneal dialysis (PD) patients to be higher, similar, or even lower when compared to rates in younger populations. We prospectively analyzed all episodes of peritonitis registered in the 381 patients (219 males, 162 females; mean age, 55.5 +/- 17.0 years) who were treated with PD during four years (1993-1996) in our multicenter group. Patients were distributed into two groups. Group A included 138 patients aged 65 years or over (mean age: 72.3 +/- 5.1 years); group B included 243 patients aged below 65 years (mean age: 46.0 +/- 13.6 years). No differences were seen in general PD characteristics. Normalized protein catabolic rate (nPCR) was higher in younger patients (p = 0.001). Patients in group A experienced more peritonitis (135 episodes; 1 episode per 16.7 patient-months) than patients in group B (198 episodes; 1 episode per 21.7 patient-months; p = 0.01). Although no differences were seen in the general characteristics of the peritonitis episodes, gram-negative peritonitis and peritonitis not achieving a cure were more commonly secondary to enteric bacteria in group A (p = 0.03). We conclude that PD patients aged 65 years or over are at higher risk of peritonitis. Also, in this age group, gram-negative peritonitis and peritonitis with any evolution except cure are more likely to be due to enteric bacteria.

Age Factors↗

Grouping together highly diverged PD-(D/E)XK nucleases and identification of novel superfamily members using structure-guided alignment of sequence profiles.

The PD-(D/E)XK nuclease domains, initially identified in type II restriction enzymes, serve as models for studying aspects of protein-DNA interactions, mechanisms of phosphodiester hydrolysis, and provide indispensable tools for techniques in genetic engineering and molecular medicine. However, the low degree of amino acid conservation hampers the possibility of identification of PD-(D/E)XK superfamily members based solely on sequence comparisons. In several proteins implicated in DNA recombination and repair the restriction enzyme-like nuclease domain has been found only after the corresponding structures were determined experimentally. Here, we identified highly diverged variants of the PD-(D/E)XK domain in many proteins and open reading frames using iterative database searches and progressive, structure-guided alignment of sequence profiles. We predicted the possible cellular function for many hypothetical proteins based on their relative similarity to characterized nucleases or observed presence of additional domains. We also identified the nuclease domain in genuine recombinases and restriction enzymes, whose homology to other PD-(D/E)XK enzymes has not been demonstrated previously. The first superfamily-wide comparative analysis, not limited to nucleases of known structure, will guide cloning and characterization of novel enzymes and planning new experiments to better understand those already studied.

Amino Acid Sequence↗

Optimising dose in peritoneal dialysis (PD).

PD dose is one determinant factor for PD adequacy. With the standard CAPD prescription of 4 x 2 L per day large patients especially after residual renal function has been lost, are at risk of being underdialysed according to the current standards. By using automated PD dialysis dose can be enhanced by individualising prescription and most of even large and anuric patients can be maintained on PD.

Biological Transport↗

Abnormalities of gonadotrophs in the adenohypophysis of infertile male PD rats.

Male PD strain rats are sterile in the homozygous condition (pd/pd) due to abnormal spermatogenesis detectable at around nine weeks of age. Previous studies have indicated electron microscopic abnormalities in the Sertoli cells of pd/pd males at three and 12 weeks of age. Since spermatogenesis and Sertoli cell function depend on gonadotropins (luteinizing and follicle-stimulating hormones [LH and FSH]) and testosterone, production and/or secretion of these hormones might be altered in pd/pd males. The aim of the study reported here was to investigate the hormonal status of pd/pd males at three, six, and nine weeks of age. Although alteration was not evident in the LH-immunoreactive cells, FSH-immunoreactive cells in pd/pd males were small in size with scant cytoplasm and were reduced in number and area (73 and 51% of phenotypically normal pd/+ males, respectively) at three weeks of age, although serum FSH concentration was similar to that in pd/+ males. At six and nine weeks of age, percentages of the areas occupied by LH- and FSH-immunoreactive cells in pd/pd males were higher than those in pd/+ males. Serum FSH concentration in pd/pd males was significantly high at nine weeks of age, although a difference in serum LH and testosterone concentration was not evident. These results suggest that FSH production in pd/pd males is decreased at three weeks of age. This might be associated with the Sertoli cell abnormalities and subsequent abnormal spermatogenesis seen in adult life.

Animals↗

[Neo-natal hyperbilirubinemia and G-6-PD Ankara deficiency, a new enzymatic variant discovered in a Turkish family (author's transl)].

A G-6-PD deficiency has been found in a Turkish male premature with neo-natal hyperbilirubinemia. His parents have no hemolytic antecedents. The propositus has a severe enzym deficiency in erythrocytes, a very decreased activity in leukocytes and platelets. His mother was heterozygous for this variant and his father had no abnormality. The deficient enzym was a new variant: G-6-PD Ankara. The main characteristics of this variant were the following: 1 degree severe enzym deficiency in erythrocytes (8% of normal); 2 degrees fast starch gel electrophoretic mobility (110% of normal); 3 degrees enzym instability in vivo and in vitro; 4 degrees increased KiNADPH; 5 degrees decreased molecular specific activity (58% of normal). Only variant B(-) G-6-PD deficiency have hitherto been described in Turkey. In contrast, G-6-PD Ankara is a fast variant and is unlike any other known variants.

Erythrocytes↗

Increased total body fat during PD treatment.

UNLABELLED: Sufficient nutritional intake is important to adjust the increased catabolic rate in uremic patients during dialysis treatment. Increased glucose absorption during PD treatment may, however, interfere with the amount of muscle- and fat-mass in the body. We have therefore studied the amount of total body fat composition in 8 male PD patients (treatment period 79 months, range 3-23 before and 165.5 months, range 8-35.5 after the study). Food intake was recorded for 7 days twice in four patients with an interval of 6-8 months. Total body fat (%) was measured by means of a computerized model of near infrared interactance (IRI) ("FUTREX") on the dominant upper arm. The energy and protein intake were 1731 +/- 292 kcal. and 86.9 +/- 17.2 g (n = 4) during the first recording period of food intake. In the second period the energy and protein intake were 1676 +/- 105 kcal and 72.7 +/- 10.2 g (n = 4) (NS). The total body fat increased from 19.8 +/- 2.9 to 22.5 +/- 3.0 (p < 0.05), in spite of unchanged total body weight. CONCLUSION: PD patients seem to accumulate fat during PD treatment with glucose as osmotic agent. This may influence the cardiovascular risks. The results indicate nutritional adjustments and possibly also increased physical activity.

Adipose Tissue↗

Ultrafiltration and small solute transport at initiation of PD: questioning the paradigm of peritoneal function.

BACKGROUND: Human peritoneal function on commencing peritoneal dialysis (PD) is not yet adequately understood. The objective of this study was to determine peritoneal functional patterns on commencing PD. METHODS: 367 end-stage renal disease (ESRD) patients on PD for the first time were studied between their initial second to sixth weeks on PD. Urea and creatinine mass transfer area coefficients (MTAC) and standardized ultrafiltration (UF) capacity were determined. RESULTS: Mean parametric values were MTAC urea 22.9 +/- 7.04 mL/min, MTAC creatinine 10.31 +/- 4.68 mL/min, and UF 896 +/- 344 mL. Gender, patient size, and diabetes or kidney disease did not affect these parameters. The relationship between values of MTAC creatinine and UF reached statistical significance, although with a low value for Pearson's coefficient (r = -0.30, p = 0.001). Age showed a significant inverse linear correlation with UF capacity (r = -0.15, p = 0.003) and MTAC urea (r = -0.11, p < 0.05). Logistic regression analysis demonstrated that UF below 400 mL was independently related to a high MTAC creatinine and older age. Diabetes was least frequent in patients with the lowest UF. However, in the analysis of MTAC creatinine quintiles, UF values did not follow the expected inverse pattern. The lack of differences in UF between the second and third to fourth MTAC creatinine quintiles is remarkable; MTAC creatinine ranged from 6.71 to 13.54. CONCLUSIONS: The functional characteristics of human peritoneum varied markedly and there was a less intense than expected relationship between solute and water transports. This mild inverse relationship is intriguing and suggestive of the necessity of redefining some basic concepts. Age was associated with a lower peritoneal UF capacity, in part independently of small solute transport.

Adult↗

Intracerebroventricular administration of PD 140.548 N-methyl-D-glucamine attenuates the release of cortisol and catecholamines induced by duodenal distension in the sheep.

The aim of this study was to determine the influence of mechanically induced duodenal distension (DD) and PD 140.548 N-methyl-D-glucamine (a specific peptide antagonist of a CCK1 receptor) premedication on mechanographical reticulo-ruminal activity, animal general behaviour, catecholamines (CA) and the blood plasma cortisol levels, as well as the clinical symptoms of visceral pain induced by DD in sheep. After 24 h fasting, 6 animals, Polish merino sheep were praeanaesthetised by i.m. injection of ketamine (20 mg x kg(-1) b.w.) and anaesthetised with i.v. infusion of pentobarbital (20 mg x kg(-1) b.w.) and a permanent stainless steel cannula (gate cannula) was inserted inside the lateral cerebral ventricle (controlled by cerebrospinal fluid efflux) 10 mm above the bregma and 5 mm laterally from the midline suture using stereotaxic method. Under the same general anaesthesia and analgesia a T-shaped silicon cannula, was inserted into the duodenum (12 cm from pylorus) and a second one was inserted into the dorsal sac of the rumen. During 7 consecutive days after surgery each animal was treated i.m. with procaine penicillin (300000 I.U..kg(-1) b.w.), dihydrostreptomycine (DHS, 10 microg x kg(-1) b.w.), prednisolone acetate 1.2 mg x kg(-1) b.w.) together and i.m. injection of ketamine (20 mg x kg(-1) b.w.), separetely. The influence of PD 140.548 N-methyl-D-glucamine on the unfavourable effects of duodenal distension using a 10 cm long balloon filled with 40 and 80 ml (DD40 and DD80) water at animal body temperature was investigated in this study. Five minutes DD40 and DD80 caused an immediate and compete inhibition of the reticulo-ruminal frequency, a significant increase in plasma CA and cortisol levels, an increase in the heart rate, hyperventilation and other symptoms of pain, proportionally to the degree of intestinal distension. Intracerebroventricular (i.c.v.) administration of PD 140.548 alone at a dose of 0.25, 0.5, 1 or 2 mg in toto did not significantly change the reticulo-ruminal motility, CA and cortisol concentrations, but 10 min after the i.c.v. infusion (or 10 min before DD) at a dose 1 and 2 mg in toto , it completely blocked the increase of blood plasma cortisol, epinephrine (E), norepinephrine (NE) and dopamine (DA) concentrations for 20 min. In the some time it prevented the reticulo-ruminal atony provocked by DD. It is concluded that PD 140.548 N-methyl-D-glucamine--an antagonist of the central CCK1 receptor can be an effective analgesic agent in duodenal pain. This action is due to the inhibition of peripheral CCK1 type receptor in the central descending nerve pathway, facilitating pain transmission in sheep perhaps in the hypothalamic-pituitary-adrenal axis.

Animals↗

An analysis of the effectiveness and benefits of peritoneal dialysis and haemodialysis using Nigerian made PD fluids.

Haemodialysis (HD) and peritoneal dialysis (PD) remains the cornerstone of management of patients with renal failure in developing countries as renal transplantation is just developing in most. Although both HD and PD are cost intensive, specific advantages and disadvantages have been identified with either of them. Comparative assessment of their effectiveness, benefits and cost will assist in providing a rational basis for preference of one or the other especially in third world countries where renal replacement therapy remains unaffordable and therefore relatively inaccessible to majority of patients. We therefore conducted this prospective randomised study to compare the effectiveness, benefits, cost and complications of acute or intermittent PD (IPD) and HD using locally manufactured PD fluids. Two groups of twenty patients with renal failure matched for age and clinical diagnosis were managed with IPD and HD and the effectiveness, costs and complications of both modalities compared. We found that both were comparably effective in the control of uraemia with significant reductions in the serum urea, creatinine and potassium from 29.2 +/- 7.2 mmol/L, 1693.7 +/- 580.5micromol/L and 4.8 +/- 1.2 mmol/L to 13.2 +/- 4.6 mmol/L, 796.0 +/- 458.0micromol/ L and 3.3 +/- 0.6 mmol/L respectively for IPD (P<0.05) and 34.4 +/- 9.0mmol/L, 1536.0 +/- 832.5 micromol/L and4.8 +/- 1.3 mmoV L to 14.6 +/- 7.5 mmol/L, 830.0 +/- 570.7 micromol/L and 3.9 +/- 0.8 mmol/L respectively for HD (P<0.05). In addition, there were significant improvements in serum bicarbonate in both groups. There was no significant difference in percentage reduction in serum urea, creatinine and serum potassium in both groups (P>0.05). However, HD managed patients required more blood transfusion (P<0.05). There were also comparably significant reductiohs in systolic, diastolic and mean arterial blood pressures in both groups (P<0.05). The costs of dialysis as well as the total cost of hospitalization were found to be significantly lower in patients managed with IPD (P<0.05). The commonest complication observed in patients managed with IPD was peritonitis while in patients managed with HD it was dialysis-induced hypotension. The clinical outcome was equally good in all the ARF patients as all of them recovered irrespective of the treatment modality; CRF patients did not fare as well with 37.5% mortality observed. We conclude that IPD and HD are effective renal replacement therapies with the former being significantly cheaper. IPD should be encouraged in our patients with ARF or acute exacerbation of chronic renal failure.

Acid-Base Equilibrium↗

Effect of PD 128763, a new potent inhibitor of poly(ADP-ribose) polymerase, on X-ray-induced cellular recovery processes in Chinese hamster V79 cells.

The modifying effects of PD 128763 (3,4-dihydro-5-methyl-1(2H)-isoquinolinone), a potent inhibitor of poly(adenosine-diphosphate (ADP)-ribose) polymerase, on radiation-induced cell killing were examined in Chinese hamster V79 cells. This compound has an IC50 value against the purified enzyme approximately 50X lower than 3-aminobenzamide (3-AB), a widely used specific inhibitor of the enzyme. Exposure of exponentially growing cells to a noncytotoxic concentration (0.5 mM) of PD 128763 for 2 h immediately following X irradiation increased their radiation sensitivity, modifying both the shoulder and the slope of the survival curve. When recovery from sublethal damage and potentially lethal damage was examined in exponential and plateau-phase cells, respectively, postirradiation incubation with 0.5 mM PD 128763 was found not only to inhibit both these processes fully, but also to enhance further the level of radiation-induced cell killing. This is in contrast to the slight effect seen with the less potent inhibitor, 3-AB. The results presented suggest that the mechanism of radiosensitization by PD 128763 is related to the potent inhibition of poly(ADP-ribose) polymerase by this compound.

Animals↗

[Radiographic evaluation of 12% Au-Ag-Pd alloy cast lower denture plates constructed by dental student as a laboratory exercise].

We evaluated 12% Au-Ag-Pd alloy cast lower denture plates prepared by dental students in laboratory exercises for casting defects. First, we determined the most suitable exposure conditions for nondestructive radiographic test of 12% Au-Ag-Pd alloy. Subsequently, 130 plates were nondestructively evaluated by radiography under the most suitable exposure conditions. In radiographic testing using X-Omat RP films (Eastman Kodak Co.) and X-Omatic Fine Screen (Eastman Kodak Co.), the most suitable exposure conditions involved a target-to-film distance of 1.9 m, tube voltage of 148 Kvp, tube current of 10 mA, and exposure time of 1.5 sec. Preliminary radiographic examination of artificial casting defects revealed semispherical defects in the diameter of 0.25 mm in 1.6 mm-thick 12% Au-Ag-Pd alloy plates and detects of 0.26 mm in 2.4 mm thick plates. In the 130 cast plates, 56 casting defects were detected. These defects were found at the left webbing part in 40 (30.8%), right webbing part in 36 (27.7%), lingual bar in 7 (5.4%), I-bar in 4 (3.0%), and at other regions of the metal frames in 3 (2.3%) cases. These results indicate that nondestructive radiographic testing is as effective in detection of casting defects in 12% Au-Ag-Pd alloy cast plates as it is in Co-Cr and Ni-Cr alloy plates. This method was also found to be effective in evaluation of the practice metal frames constructed by dental students.

Dental Casting Technique↗