Biomedical subjects

Q Qi

Publications and source records attributed to Q Qi.

At least 19 recordsLinked to original sources

PubMed2006

Detection of Hong Kong 97-like H5N1 influenza viruses from eggs of Vietnamese waterfowl.

Three H5N1 influenza viruses were isolated from shell washes of duck and goose eggs confiscated from travelers coming from Vietnam. All eight gene segments of these viruses share high sequence identity with the H5N1 avian influenza viruses that caused outbreaks in poultry and humans in Hong Kong in 1997. Animal studies indicate that these isolated viruses are able to replicate in mouse lung and could be found in the organs of ducks without causing any clinical signs or death. However, the viruses are highly pathogenic for chickens. Although the source of these recently isolated Hong Kong 97-like H5N1 viruses is undetermined, their detection in the egg shell of duck and goose suggests that this particular genotype of H5N1 virus may have re-emerged in nature or may have been circulating continuously.

Animals↗

PubMed2001

Matrix-assisted in vitro refolding of Pseudomonas aeruginosa class II polyhydroxyalkanoate synthase from inclusion bodies produced in recombinant Escherichia coli.

In order to facilitate the large-scale preparation of active class II polyhydroxyalkanoate (PHA) synthase, we constructed a vector pT7-7 derivative that contains a modified phaC1 gene encoding a PHA synthase from Pseudomonas aeruginosa possessing six N-terminally fused histidine residues. Overexpression of this phaC1 gene under control of the strong Ø10 promoter was achieved in Escherichia coli BL21(DE3). The fusion protein was deposited as inactive inclusion bodies in recombinant E. coli, and contributed approx. 30% of total protein. The inclusion bodies were purified by selective solubilization, resulting in approx. 70-80% pure PHA synthase, then dissolved and denatured by 6 M guanidine hydrochloride. The denatured PHA synthase was reversibly immobilized on a Ni(2+)-nitrilotriacetate-agarose matrix. The matrix-bound fusion protein was refolded by gradual removal of the chaotropic reagent. This procedure avoided the aggregation of folding intermediates which often decreases the efficiency of refolding experiments. Finally, the refolded fusion protein was eluted with imidazole. The purified and refolded PHA synthase protein showed a specific enzyme activity of 10.8 m-units/mg employing (R/S)-3-hydroxydecanoyl-CoA as substrate, which corresponds to 27% of the maximum specific activity of the native enzyme. The refolding of the enzyme was confirmed by CD spectroscopy. Deconvolution of the spectrum resulted in the following secondary structure prediction: 10% alpha-helix, 50% beta-sheet and 40% random coil. Gel filtration chromatography indicated an apparent molecular mass of 69 kDa for the refolded PHA synthase. However, light-scattering analysis of a 10-fold concentrated sample indicated a molecular mass of 128 kDa. These data suggest that the class II PHA synthase is present in an equilibrium of monomer and dimer.

Acyltransferases↗

PubMed2001

Induction of unspliced c-fos messenger RNA in rodent brain by kainic acid and lipopolysaccharide.

The c-fos transcriptional factor forms an activator protein-1 (AP-1) complex with proteins from the Jun family, which plays an important role in the central nervous system. The responses of AP-1 transcriptional factors induced by kainic acid (KA) treatment have been well studied, although the transcriptional regulation of these KA-induced factors has not been clearly characterized. To investigate the role of different stimuli in controlling of the splicing of c-fos mRNA, we performed reverse transcriptional polymerase chain reaction. The results showed that spliced and unspliced c-fos is present in rat brain following KA treatment and in lipopolysaccharide (LPS)-treated primary mouse cortical brain cell cultures. Furthermore, tyrosine kinase and protein phosphatase inhibitors alter the preponderance of c-fos transcripts following LPS treatment.

Animals↗

PubMed2001

Identification of a new urinary metabolite of carbon disulfide using an improved method for the determination of 2-thioxothiazolidine-4-carboxylic acid.

A new method is reported for the analysis of 2-thioxothiazolidine-4-carboxylic acid (TTCA) in urine that is amenable to automation and provides greatly simplified chromatograms. The method comprises the addition of tetrahydro-2-thioxo-2H-1,3-thiazine-4-carboxylic acid, which is chemically similar to TTCA, as internal standard, purification on an Oasis HLB solid-phase extraction column, and analysis by HPLC with UV detection. The limit of detection for TTCA was 40 pmol/mL of urine, recovery was 79.3 +/- 1.0%, and detection was linear over at least 3 orders of magnitude. In addition, during the analysis of urine samples from workers exposed to CS(2), a novel urinary metabolite of CS(2) was recognized. The new metabolite demonstrated a dose response, was present at approximately 30% the level of TTCA, and was charaterized to be 2-thioxothiazolidin-4-ylcarbonylglycine (TTCG). Administration of TTCG to rats resulted in excretion of TTCA suggesting that TTCG is a likely precursor of TTCA. Although urinary excretion of both TTCA and TTCG resulted from administration of captan, only TTCA was detected following administration of methyl isothiocyanate. The greater selectivity of TTCG suggests that co-analysis of TTCA and TTCG in urine may aid in differentiating exposures to CS(2), captan and isothiocyanates.

Animals↗

PubMed2001

Polyhydroxybutyrate biosynthesis in Caulobacter crescentus: molecular characterization of the polyhydroxybutyrate synthase.

Caulobacter crescentus was investigated with respect to polyhydroxybutyrate (PHB) biosynthesis. Polyhydroxyalkanoate (PHA) accumulation contributing to approximately 18% of the cell dry weight was obtained in the presence of glucose. Gas chromatography-mass spectrometry and gel permeation chromatography of the purified PHA showed that this polyester was solely composed of 3-hydroxybutyrate and had a weight average molar mass of 5.5 x 10(5) g mol(-1) and a polydispersity of 1.6. An ORF encoding a conserved, hypothetical protein which shared approximately 47% identity with the PHB synthase from Azorhizobium caulinodans was identified within the complete C. crescentus genomic sequence. This putative C. crescentus PHB synthase gene, phaC, consisted of a 2019 nt stretch of DNA (encoding 673 aa residues), which encoded a PHB synthase with a molecular mass of approximately 73 kDa. This is currently the largest PHA synthase identified. The phaC coding region was subcloned into vector pBBR1-JO2 under lac promoter control. The resulting plasmid, pQQ4, mediated PHB accumulation in the mutant Ralstonia eutropha PHB(-)4 and recombinant Escherichia coli JM109(pBHR69), which produced the beta-ketothiolase and acetoacetyl-CoA reductase from R. eutropha, contributing to approximately 62% and 6% of cell dry weight, respectively. Functional expression of the coding region of phaC was confirmed by immunoblotting and in vitro PHB synthase activity.

Acyltransferases↗

PubMed2001

Parathyroid hormone/parathyroid hormone-related peptide type 1 receptor in human bone.

The parathyroid hormone/parathyroid hormone-related peptide (PTH/PTHrP) receptor (denoted as PTH-1R) is a key signaling factor through which calcium-regulating hormones PTH and PTHrP exert their effects on bone. There are contradictory reports regarding the capability of osteoclasts to express PTH-1R. To address this issue in humans, bone biopsy specimen samples from 9 normal controls and 16 patients with moderate to severe secondary renal hyperparathyroid bone disease (2 degrees HPT) with elevated PTH levels were studied to determine whether osteoclasts in the bone microenvironment express PTH-1R messenger RNA (mRNA) and protein. We report that osteoclasts express the PTH-1R mRNA but the protein is detected only in patients with 2 degrees HPT. The PTH-1R mRNA and protein also were found in osteoblasts, osteocytes, and bone marrow cells. Receptor expression was higher in osteoclasts and osteoblasts of patients with 2 degrees HPT than normal controls (98.0 +/- 1.1% vs. 65.7 +/- 14.3% and 65.8 +/- 3.4% vs. 39.1 +/- 6.2%; p < 0.01, respectively). Approximately half of osteoclasts found in bone of patients with 2 degrees HPT have the PTH-1R protein. In patients with 2 degrees HPT, a positive relationship exists between erosion depth, a parameter of osteoclastic activity, and the percentage of osteoclasts with PTH-1R protein (r = 0.58; p < 0.05). In normal controls, an inverse relationship exists between the percentage of osteoblasts with receptor mRNA, mRNA signals/cell, and serum PTH levels (r = -0.82 and p < 0.05 and r = -0.78 and p < 0.01, respectively). The results provide the novel evidence of PTH-1R in human osteoclasts and suggest a functional role for the receptors in 2 degrees HPT.

Adult↗

PubMed2001

[Measurement of formaldehyde in disinfectant with spectrophotometry].

Formaldehyde in disinfectant was measured by acetylacetone spectrophotometry. The regression equation was linear when the formaldehyde concentration was smaller than 10 micrograms/ml. The detection limit was 0.08 microgram/ml. The accuracy was less than 3.9% and the recovery varied between 100.2%-108.2% for formaldehyde disinfectant with different concentration, which was similar to titrimetry. It was demonstrated that the method was simple, reproducible, sensitive, precise and accurate, making it important for assay of formaldehyde in disinfectant when disturbance caused titrimetry unavailable.

Disinfectants↗

PubMed2001

[Acoustic analysis in patients with trauma to unilateral cricoarytenoid joint by computer technique].

OBJECTIVE: To investigate the acoustic characteristics of unilateral cricoarytenoid joint trauma and evaluate the effect of acoustic analysis technique on the diagnosis and treatment of this disease. METHOD: The voice signals of sustained vowel [a] were measured using a micro-computer with Dr. Speech software in 50 healthy adults and 30 patients with unilateral cricoarytenoid joint trauma. The acoustic parameters (jitter, shimmer and NNE) and spectrographic characteristics (harmonic waves, formants and noise) were analyzed. The acoustic changes before and after the treatment of arytenoid motion were observed and compared. RESULT: All acoustic parameters were significantly increased in trauma of unilateral cricoarytenoid joint. The pathologic spectrograph showed decrease or loss of harmonic waves and formants, and increase of noise, in middle and high frequencies. There was a relationship between NNE and the position of the vocal cord. After the treatment of arytenoid motion, 33% patients were cured and had normal acoustic parameters and spectrograph. 47% were improved with reduced parameters and improved spectrograph. The acoustics in 20% cases didn't change at all after treatment. The acoustic parameters were significantly decreased after the treatment of arytenoid motion. CONCLUSION: The present study suggested that the acoustic parameters may estimating the degrees of voice lesion as objective standards and NNE may judge the degree of glottic closure. Both acoustic parameters and spectrograph are of value in the diagnosis, treatment effect and prognosis observation to cricoarytenoid joint trauma.

Adolescent↗

PubMed2001

[Advances on the biological effect indices for fine particles (PM2.5) in air].

Fine particles are complex mixture of air pollutants containing not only a great deal of organic compounds but also varied kind of metals, such as B(a)p, Pb, Cd, Cr etc. Most of those compounds are toxic. Some of them are the cause of lung inflammation and asthma, some are genotoxic with a potential of carcinogenesis. Because the fine particles can be inhaled into lung and deposit in lung tissue, which have adverse effects on human health. Epidemiological studies indicated that increased mortality and morbidity, especially for cardiovascular and lung diseases, was associated with the amount of ambient fine particles. Although some scientists thought fine particles damaging the body through oxidant stress, inflammation and genetic materials and so on, the mechanism for them is not known well. Therefore, it is necessary to explore the biological effects of fine particle on human health in the future.

Air Pollutants↗

PubMed2000

Cloning and expression of MP13 gene from rat hippocampus, a new factor related to guanosine triphosphate regulation.

C-Fos and the Fos-related antigens (FRA) are induced by various stimuli. A novel 35-37 kDa FRA was induced much longer after the treatment using kainic acid (KA) and may be very important for neuronal survival after brain damage. To identify this long-term FRA, we have constructed a cDNA library derived from hippocampus after KA treatment and screened it with an antibody highly conserved M-peptide region of FRAs. One gene, MP13, was cloned with a 1662 bp open reading frame and coded for a 554-amino acid protein. MP13 has a leucine zipper region, a glutamine repeat region, and has high similarity to the activator of the small guanosine triphosphate (GTP)ase Rab5. Gel retardation analysis revealed that MP13 functions as a GTP regulation related factor.

Amino Acid Sequence↗

PubMed2000

Molecular cloning, genomic organization, and biochemical characterization of myristoyl-CoA:protein N-myristoyltransferase from Arabidopsis thaliana.

Myristoyl-CoA:protein N-myristoyltransferase (NMT, EC 2.3.1.97) catalyzes the co-translational addition of myristic acid to the amino-terminal glycine residue of a number of important proteins of diverse functions. We have isolated a full-length Arabidopsis thaliana cDNA encoding NMT (AtNMT1), the first described from a higher plant. This AtNMT1 cDNA clone has an open reading frame of 434 amino acids and a predicted molecular mass of 48,706 Da. The primary structure is 50% identical to the mammalian NMTs. Analyses of Southern blots, genomic clones, and database sequences suggested that the A. thaliana genome contains two copies of NMT gene, which are present on different chromosomes and have distinct genomic organizations. The recombinant AtNMT1 expressed in Escherichia coli exhibited a high catalytic efficiency for the peptides derived from putative plant myristoylated proteins AtCDPK6 and Fen kinase. The AtNMT was similar to the mammalian NMTs with respect to a relative specificity for myristoyl CoA among the acyl CoA donors and also inhibition by the bovine brain NMT inhibitor NIP(71). The AtNMT1 expression profile indicated ubiquity in roots, stem, leaves, flowers, and siliques (approximately 1.7 kb transcript and approximately 50 kDa immunoreactive polypeptide) but a greater level in the younger tissue, which are developmentally very active. NMT activity was also evident in all these tissues. Subcellular distribution studies indicated that, in leaf extracts, approximately 60% of AtNMT activity was associated with the ribosomal fractions, whereas approximately 30% of the activity was observed in the cytosolic fractions. The NMT is biologically important to plants, as noted from the stunted development when the AtNMT1 was down-regulated in transgenic Arabidopsis under the control of an enhanced CaMV 35S promoter. The results presented in this study provide the first direct molecular evidence for plant protein N-myristoylation and a mechanistic basis for understanding the role of this protein modification in plants.

Acyltransferases↗

PubMed2000

In vitro synthesis of poly(3-hydroxydecanoate): purification and enzymatic characterization of type II polyhydroxyalkanoate synthases PhaC1 and PhaC2 from Pseudomonas aeruginosa.

For the first time, the purification has been achieved of the type II polyhydroxyalkanoate (PHA) synthases PhaC1 and PhaC2 from Pseudomonas aeruginosa applying N-terminal His6-tag fusions and metal chelate affinity chromatography. In vivo His6-tagged PHA synthase activity was confirmed by functional expression of the corresponding genes in Escherichia coli, and PHA synthase activity could also be measured in vitro with the enzymes. The specific enzyme activity of PHA synthases PhaC1 and PhaC2 was 0.039 U mg(-1) and 0.035 U mg(-1) protein, respectively. Kinetic studies showed a lag phase for both PHA synthases using (R,S)-3-hydroxydecanoyl-CoA as substrate. Specific enzyme activity was increased to 0.055 U mg(-1) when the phasin GA24 from Ralstonia eutropha was added to the assay. CoA inhibited PHA synthase activity, and a Ki of 85 microM was determined. A two-enzyme system was established, employing commercially available acyl-CoA synthetase and PHA synthase, which allowed the in vitro de novo PHA granule formation and the in vitro synthesis of poly(3-hydroxydecanoate) exhibiting a weight average molar mass of 9.8 x 10(4) g mol(-1), and which occurred independently of pre-existing PHA granules.

Acyltransferases↗

PubMed2000

[Application of the fluorescent in situ hybridization on the prenatal diagnosis of the fetal aneuploidy in the uncultured amniocytes].

OBJECTIVE: To study the method and value of fluorescent in situ hybridization (FISH) on the rapid prenatal diagnosis of the fetal aneuploidy in the uncultured amniocytes. METHODS: Amniocentesis was performed in 20 pregnant women of 16-36 gestational weeks with indications of prenatal diagnosis. We performed FISH, respectively, with the biotin labelled chromosome X and 18 centromeric probes and the digoxin labelled chromosome Y centromeric and 21q11 and 13q14-q21 specific probes on the uncultured amniocytes. The slides were observed under the fluorescent microscope and the images were captured by the Applied Imaging System. RESULTS: Normal chromosome number was observed in 19 cases: 10 cases of 46, XX and 9 cases of 46, XY. Aneuploidy was found in 1 case which was 46, XY/47, XXY and proved by G-banding chromosomal on cord blood. CONCLUSION: Fetal aneuploidy could be diagnosed within 24 hours after the amniocentesis by FISH. FISH is a rapid, accurate and reliable method to detect fetal aneuphoidy in uncultured amniocytes.

Adult↗

PubMed2000

[Radiographic studies of cervical spine motion range in normal Chinese subjects with computer-assisted image analysis: full flexion and extension].

OBJECTIVES: To study the degenerative regularity of normal Chinese cervical spine by observing the motion range of full cervical flexion and extension, and to provide evidences for further investigation of cervical segmental instability. METHODS: 764 X-ray plain films of full cervical flexion and extension in 382 normal Chinese subjects (214 were male and 168 female) were investigated using self-designed cervical X-ray image analysis system. The subjects within the same sex group were divided into three groups according to the age: group A (20 years to 39 years), group B (40 years to 59 years) and group C (60 years to 76 years). During the full cervical flexion and extension motion, total intervertebral motion range (from C(2) - C(3) to C(6) - C(7)) and intervertebral motion range at each level were major parameters. RESULTS: The range of total intervertebral motion showed much greater mobility in group A than in group B and group C (P < 0.01) but no statistically significant difference between group B and group C (P > 0.05). The range of intervertebral motion was maximal at C(5) - C(6) in group A. The place of maximal motion shifted to the C(4) - C(5) in both group B and group C. C(2) - C(3) showed minimal mobility in all three groups. There was no statistically significant difference (P > 0.05) between male and female. CONCLUSIONS: The motion range and degenerative regularity of normal Chinese cervical spine were similar in either sex. The range of total intervertebral motion (from C(2) - C(3) to C(6) - C(7)) had a tendency to decrease rapidly and then became steady with age. For the range of intervertebral motion, the place of maximal motion shifted to the higher level with age from C(5) - C(6) in group A to C(4) - C(5) in group B and group C.

Adult↗

PubMed2000

[Influence of solid thoracolumbar kyphosis on lumbar spine and surgical treatment].

OBJECTIVE: To investigate the influence of solid thoracolumbar kyphosis on the lumbar spine and surgical treatment. METHODS: 14 had solid kyphosis of the thoracolumbar spine. Cobb angle of kyphosis of the thoracolumbar spine and lordosis between L(2)/S(1), L(2)/L(5), L(2)/L(3), L(3)/L(4), L(4)/L(5), L(5)/S(1) pre- and post-osteotomy was measured respectively, and the amount of vertebrae slipped over 3mm was recorded. The results were compared with those of the normal group respectively. RESULTS: The Cobb angles of lordosis between L(2)/S(1), L(2)/L(5), L(2)/L(3), L(3)/L(4), L(4)/L(5), L(5)/S(1) in the deformity group were increased significantly compared with those that of the normal group respectively; obvious changes in percentage occurred in the segment between L(2)/L(3) and L(3)/L(4). Over lordosis of the lumbar spine was greatly corrected postosteotomy of the thoracolumbar spine, it was still significantly different compared with that of the normal group. In 9 patients with retrolisthesis of 20 vertebrae, 70% occurred in L(2) and L(3) vertebrae. The amount of retrolisthesis of vertebrae decreased to 3 in two patients. No retrolisthesis of vertebra was seen in the normal group. Single-stage procedures combined with anterior releasing and posterior osteotomy through facet joints for kyphosis of the thoracolumbar spine showed a correction. rate of 85.7%, but single-stage osteotomy through the posterior vertebra showed a correction rate of 60.7%. Seven of 8 patients who had had seriously back pain complained of no pain or slight backache after operation. 40% of the patients showed functional improvement in the sphincter of the urinary bladder and anus. 50% of the patients had improvement in muscle strength. CONCLUSIONS: Kyphosis of the thoracolumbar spine may result in over lordosis of the lumbar spine and retrolisthesis of vertebrae, which are obvious in the upper lumbar spine. These changes may lead to back pain. Correction of kyphosis of the thoracolumbar spine may obviously decrease over lordosis of the lumbar spine and inclination of vertebral slip, and may further decrease the overload to the posterior column of the spine and relieve back pain. Osteotomy combined with anterior and posterior procedures is effective and safe in the correction of kyphosis of the thoracolumbar spine.

Adolescent↗

PubMed2000

[Ultrastructure of the lymph capillaries in human dental pulp].

OBJECTIVE: The purpose of this article is to observe the ultrastructures of the lymph capillaries in the human dental pulps. METHODS: Investigations have been performed on dental pulps from 8 human permanent teeth, including 4 mandibular first premolars and 4 maxillary first premolars, which were extracted for orthodontic reason. As soon as possible, we cleaved the teeth longitudinally and immersed in the fixative solution at 4 degrees C for 1 hour, then kindly removed the pulps and immersed in the same fixative solution for 3 hours, then routinely postfixed, dehydrated, embedded, and prepared the ultrathin sections (50-70 nm) without semithin section localization. The lymph vessels were distinguished from blood vessels on ultrathin sections by their morphological features. RESULTS: We have observed three fundamental kinds of intercellular junctions, overlapping(51%), end to end(36.1%), and interdigistating (10.6%). A few complex junctions also could be seen, but we failed to find the open junction. The Weibel-Palade bodies were occasionally present in the lymphatic vessels endothelial cells of young dental pulps. And we even found the lipofuscins in the cytoplasm of the endothelium. Some inclusion bodies, such as paracrystalline inclusions and myeloid bodies, also could be seen. There were many micropinocytotic vesicles in the cytoplasm of the lymphatic endothelium, the diameter of the most vesicles was about 50-80 nm, some was about 100-500 nm. Some vesicles appeared to lie free within the cytoplasm, and some were seen to touch or open onto the luminal or abluminal surfaces of the endothelia, which suggested that many vesicles were not simple discrete units but rather from parts of chains that reached either luminal or abluminal surfaces. It was reported that micropinocytotic vesicles, open junctions and intraparietal channels provided fluid transport. CONCLUSION: Dental pulp is a special organ, and the lymph capillaries in it have their own ultrastructural features.

Adolescent↗

PubMed1999

Effects of antisense repression of an Arabidopsis thaliana pyruvate dehydrogenase kinase cDNA on plant development.

Pyruvate dehydrogenase kinase (PDHK), a negative regulator of the mitochondrial pyruvate dehydrogenase (PDH) complex (mtPDC), plays a pivotal role in controlling mtPDC activity, and hence, the TCA cycle and cell respiration. This report describes the cloning of a pyruvate dehydrogenase kinase cDNA (AtPDHK) from Arabidopsis thaliana and focuses on the effects of antisense down-regulation of its expression on plant growth and development. The deduced amino acid sequence of AtPDHK exhibits extensive similarity to other plant and mammalian PDHKs, containing conserved domains typical of two-component histidine protein kinases. The Escherichia coli expressed AtPDHK specifically phosphorylated mammalian PDH E1 in a time-dependent manner. Antisense expression of the AtPDHK cDNA led to marked elevation of mtPDC activity in transgenic plants with increases ranging from 137% to 330% compared to control plants. Immunoblot analyses performed with a monoclonal antibody to the E1alpha mtPDH component (the subunit phosphorylated by PDHK) indicated that the increased mtPDC activity was not the result of an increase in the level of PDH protein. MtPDC from transgenic plants showed a reduced sensitivity to ATP-dependent inactivation compared to that observed in wild-type plants. Collectively, these data suggest that the antisense partial silencing of the negative regulator, PDHK, was responsible for the increased mtPDC activity observed in the antisense PDHK plants. Transgenic plants with partially repressed AtPDHK also displayed altered vegetative growth with reduced accumulation of vegetative tissues, early flower development and shorter generation time. The potential role for AtPDHK gene manipulation in crop improvement is discussed.

Arabidopsis↗

PubMed1999

22-oxacalcitriol suppresses secondary hyperparathyroidism without inducing low bone turnover in dogs with renal failure.

BACKGROUND: Calcitriol therapy suppresses serum levels of parathyroid hormone (PTH) in patients with renal failure but has several drawbacks, including hypercalcemia and/or marked suppression of bone turnover, which may lead to adynamic bone disease. A new vitamin D analogue, 22-oxacalcitriol (OCT), has been shown to have promising characteristics. This study was undertaken to determine the effects of OCT on serum PTH levels and bone turnover in states of normal or impaired renal function. METHODS: Sixty dogs were either nephrectomized (Nx, N = 38) or sham-operated (Sham, N = 22). The animals received supplemental phosphate to enhance PTH secretion. Fourteen weeks after the start of phosphate supplementation, half of the Nx and Sham dogs received doses of OCT (three times per week); the other half were given vehicle for 60 weeks. Thereafter, the treatment modalities for a subset of animals were crossed over for an additional eight months. Biochemical and hormonal indices of calcium and bone metabolism were measured throughout the study, and bone biopsies were done at baseline, 60 weeks after OCT or vehicle treatment, and at the end of the crossover period. RESULTS: In Nx dogs, OCT significantly decreased serum PTH levels soon after the induction of renal insufficiency. In long-standing secondary hyperparathyroidism, OCT (0.03 microg/kg) stabilized serum PTH levels during the first months. Serum PTH levels rose thereafter, but the rise was less pronounced compared with baseline than the rise seen in Nx control. These effects were accompanied by episodes of hypercalcemia and hyperphosphatemia. In animals with normal renal function, OCT induced a transient decrease in serum PTH levels at a dose of 0.1 microg/kg, which was not sustained with lowering of the doses. In Nx dogs, OCT reversed abnormal bone formation, such as woven osteoid and fibrosis, but did not significantly alter the level of bone turnover. In addition, OCT improved mineralization lag time, (that is, the rate at which osteoid mineralizes) in both Nx and Sham dogs. CONCLUSIONS: These results indicate that even though OCT does not completely prevent the occurrence of hypercalcemia in experimental dogs with renal insufficiency, it may be of use in the management of secondary hyperparathyroidism because it does not induce low bone turnover and, therefore, does not increase the risk of adynamic bone disease.

Animals↗