Enantiomeric separation of a moxifloxacin intermediate by chiral liquid chromatography using cellulose based stationary phases.
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Anti-Infective Agents↗
Biomedical subjects
D S Rao
Publications and source records attributed to D S Rao.
LC method for the quantitative determination of oxaprozin and its impurities in the bulk drug.
A reversed phase linear gradient liquid chromatographic method was developed for the separation and quantitative determination of the seven known process related impurities and one degraded product of oxaprozin in the bulk drug material. An Inertsil-ODS 3V (150 x 4.6 mm), 5 microm column was operated with a phosphate buffer acetonitrile gradient. Detection was carried out on a UV detector at 254 nm. This method has been proved to be accurate and sensitive. The limits of detection (LOD) and limits of quantification (LOQ) of impurities were in the order of 5-60 ng and 16-200 ng, respectively. In addition to its ruggedness and robustness, this method offers identification of all eight impurities in a single run.
Anti-Inflammatory Agents, Non-Steroidal↗
Randomized trial of parathyroidectomy in mild asymptomatic primary hyperparathyroidism: patient description and effects on the SF-36 health survey.
BACKGROUND: The treatment of patients with asymptomatic primary hyperparathyroidism remains controversial despite a National Institutes of Health consensus statement. This statement also recommended a randomized clinical trial because none exists to address this issue. METHODS: Informed consent was obtained from 53 asymptomatic patients with confirmed asymptomatic primary hyperparathyroidism who participated in this randomized trial of parathyroidectomy versus observation. Patients completed the SF-36 Health Survey, an instrument that measures wellness, every 6 months for 2 years. Average annual changes were compared. RESULTS: Fifty-three patients (42 female, 11 male) with asymptomatic, mild (serum calcium level, 10.1-11.5 mg/dL) asymptomatic primary hyperparathyroidism who agreed to participate were randomized into either a surgical group or an observation group. The mean calcium level was 10.31 mg/dL. The only demographic difference between groups was age, with the operative group being older (66.7 vs 62.6 years; P <.03). The scores on 2 of the 9 domains of the SF-36 were significantly different (P <.007 and <.012, respectively); both favored the operative group. CONCLUSIONS: Improved function is seen after parathyroidectomy when compared with patients who did not undergo operation. This study supports surgical management of mild primary hyperparathyroidism at the time of diagnosis because many patients have reversible nonclassic symptoms of the disease.
Aged↗
Effect of vitamin D nutrition on parathyroid adenoma weight: pathogenetic and clinical implications.
In primary hyperparathyroidism, adenoma size is a major determinant of disease severity and manner of presentation, but the reason for the large variation in size (>100-fold) is unknown. One factor could be the level of vitamin D nutrition, because in India, where vitamin D deficiency is endemic, adenomas are larger and the disease more severe than in the U.S. Accordingly, we determined the relationship between vitamin D nutrition, as measured by serum levels of 25-hydroxyvitamin D (25OHD), and parathyroid gland weight, expressed on a logarithmic scale, in 148 U.S. patients with primary hyperparathyroidism. A significant inverse relationship was found between log gland weight as dependent variable and serum 25OHD as independent variable (r = -0.365; P < 0.0001). The only other influence on gland weight was a weak inverse correlation with age. Log gland weight as an independent variable was significantly related to adjusted calcium, PTH, and alkaline phosphatase (AP) as dependent variables. In 51 patients with serum 25OHD levels less than 15 ng/mL, gland weight, PTH, AP, and adjusted calcium were each significantly higher than in 97 patients with 25OHD levels of 15 ng/mL or more, but 1,25-dihydroxyvitamin D levels were similarly increased in both groups. In the former group the response of adjusted calcium to PTH was blunted, and the response of AP was enhanced, based on significant differences in regression slopes (P = 0.0004 and 0.0022, respectively). Suboptimal vitamin D nutrition stimulates parathyroid adenoma growth by a mechanism unrelated to hypocalcemia or 1,25-dihydroxyvitamin D deficiency and reduces the calcemic response to PTH, so that a higher PTH level and more parathyroid cells are needed to raise the patient's serum calcium to the level corresponding to the increased set-point that is characteristic of the disease. Improved vitamin D nutrition in the population is partly, perhaps largely, responsible for the historical changes in disease severity and manner of presentation that have occurred over the last 50 yr.
Adenoma↗
Is there a difference between right and left femoral bone density?
Because of the known differences in bone mineral density (BMD) of the dominant and nondominant forearms, it has been customary to measure BMD of the nondominant forearm to reduce variance. However, it is less clear whether such systematic differences exist between BMD of the two hips. Accordingly, we measured BMD of both hips and the spine in 131 consecutive white women who presented to a community based private practitioner for evaluation and advice on osteoporosis. There was a highly significant correlation between BMD of the two hips at the femoral neck, trochanter, and Ward's triangle (r = 0.91, 0.93, and 0.89; p < 0.0001 for all three sites), and also between BMD at various measurement sites in the hip and the spine BMD (p < 0.0001). Although, there was no significant difference between the right and left femoral neck BMD, there were small (approximately 1-2.5%) but significant differences between BMD of the two hips at the trochanter and Ward's triangle (p = 0.008 and 0. 005, respectively). The left hip BMD was consistently higher than the right hip BMD at all measurement sites. Because of the small sample size of the left-handed persons, we were unable to determine the influence of dominant handedness on hip BMD. We concluded the following: (1) BMDs of the two hips are highly correlated at relevant measurement sites; (2) there does not appear to be a dominant hip as there is dominant forearm; (3) because of strong agreement between BMD of the two hips there is little justification to measure both hips in routine clinical practice.
Adult↗
Anomalous origins of right coronary and left anterior descending coronary arteries: angiographic profiles.
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Coronary Angiography↗
Emerging role of cardiac troponins in acute coronary syndromes.
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Coronary Disease↗
Isolation and identification of 1alpha-hydroxy-24-oxovitamin D3 and 1alpha,23-dihydroxy-24-oxovitamin D3: metabolites of 1alpha,24(R)-dihydroxyvitamin D3 produced in rat kidney.
1alpha,24(R)-Dihydroxyvitamin D3 [1alpha,24(R)(OH)2D3], a synthetic vitamin D3 analog, has been developed as a drug for topical use in the treatment of psoriasis. At present, the target tissue metabolism of 1alpha,24(R)(OH)2D3 is not understood completely. In our present study, we investigated the metabolism of 1alpha,24(R)(OH)2D3 in the isolated perfused rat kidney. The results indicated that 1alpha,24(R)(OH)2D3 is metabolized in rat kidney into several metabolites, of which 1alpha,24(R),25-trihydroxyvitamin D3, 1alpha,25-dihydroxy-24-oxovitamin D3, 1alpha,23(S),25-trihydroxy-24-oxovitamin D3, and 1alpha,23-dihydroxy-24,25,26,27-tetranorvitamin D3 are similar to the previously known metabolites of 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3]. In addition to these aforementioned metabolites, we also identified two new metabolites, namely 1alpha-hydroxy-24-oxovitamin D3 and 1alpha,23-dihydroxy-24-oxovitamin D3. The two new metabolites do not possess the C-25 hydroxyl group. Thus, the metabolism of 1alpha,24(R)(OH)2D3 into both 25-hydroxylated and non-25-hydroxylated metabolites suggests that 1alpha,24(R)(OH)2D3 is metabolized in the rat kidney through two pathways. The first pathway is initiated by C-25 hydroxylation and proceeds further via the C-24 oxidation pathway. The second pathway directly proceeds via the C-24 oxidation pathway without prior hydroxylation at the C-25 position. Furthermore, we demonstrated that rat kidney did not convert 1alpha-hydroxyvitamin D3 [1alpha(OH)D3] into 1alpha,25(OH)2D3. This finding indicates that the rat kidney does not possess the classical vitamin D3-25-hydroxylase (CYP27) activity. However, from our present study it is apparent that prior hydroxylation of 1alpha(OH)D3 at the C-24 position in the 'R' orientation allows 25-hydroxylation to occur. At present, the enzyme responsible for the C-25 hydroxylation of 1alpha,24(R)(OH)2D3 is unknown. Our observation that the side chain of 1alpha,24(R)(OH)2D3 underwent 24-ketonization and 23-hydroxylation even in the absence of the C-25 hydroxyl group suggests that 1alpha,25(OH)2D3-24-hydroxylase (CYP24) can perform some steps of the C-24 oxidation pathway without prior C-25 hydroxylation. Thus, we speculate that CYP24 may be playing a dual role in the metabolism of 1alpha,24(R)(OH)2D3.
Animals↗
Physiological significance of C-28 hydroxylation in the metabolism of 1alpha,25-dihydroxyvitamin D(2).
In our previous study, we indicated for the first time that C-28 hydroxylation plays a significant role in the metabolism of 1alpha, 25-dihydroxyvitamin D(2) [1alpha,25(OH)(2)D(2)] by identifying 1alpha,24(S),25,28-tetrahydroxyvitamin D(2) [1alpha,24(S),25, 28(OH)(4)D(2)] as a major renal metabolite of 1alpha,25(OH)(2)D(2) [G. S. Reddy and K-Y. Tserng Biochemistry 25, 5328-5336, 1986]. The present study was performed to establish the physiological significance of C-28 hydroxylation in the metabolism of 1alpha, 25(OH)(2)D(2). We perfused rat kidneys in vitro with 1alpha, 25(OH)(2)[26,27-(3)H]D(2) (5 x 10(-10)M) and demonstrated that 1alpha,24(R),25-trihydroxyvitamin D(2) [1alpha,24(R),25(OH)(3)D(2)] and 1alpha,24(S),25,28(OH)(4)D(2) are the only two major physiological metabolites of 1alpha,25(OH)(2)D(2). In the same perfusion experiments, we also noted that there is no conversion of 1alpha,25(OH)(2)D(2) into 1alpha,25,28-trihydroxyvitamin D(2 )[1alpha,25,28(OH)(3)D(2)]. Moreover, 1alpha,24(S),25,28(OH)(4)D(2) is not formed in the perfused rat kidney when synthetic 1alpha,25, 28(OH)(3)D(2) is used as the starting substrate. This finding indicates that C-28 hydroxylation of 1alpha,25(OH)(2)D(2) occurs only after 1alpha,25(OH)(2)D(2) is hydroxylated at C-24 position. At present the enzyme responsible for the C-28 hydroxylation of 1alpha, 24(R),25(OH)(3)D(2) in rat kidney is not known. Recently, it was found that 1alpha,25(OH)(2)D(3)-24-hydroxylase (CYP24) can hydroxylate carbons 23, 24, and 26 of various vitamin D(3) compounds. Thus, it may be speculated that CYP24 may also be responsible for the C-28 hydroxylation of 1alpha,24(R),25(OH)(3)D(2) to form 1alpha, 24(S),25,28(OH)(4)D(2). The biological activity of 1alpha,24(S),25, 28(OH)(4)D(2), determined by its ability to induce intestinal calcium transport and bone calcium resorption in the rat, was found to be almost negligible. Also, 1alpha,24(S),25,28(OH)(4)D(2) exhibited very low binding affinity toward bovine thymus vitamin D receptor. These studies firmly establish that C-28 hydroxylation is an important enzymatic reaction involved in the inactivation of 1alpha,25(OH)(2)D(2) in kidney under physiological conditions.
Animals↗
Isolation and identification of 4,25-dihydroxyvitamin D2: a novel A-ring hydroxylated metabolite of vitamin D2.
Vitamin D2 is less toxic in rats when compared to vitamin D3. Our laboratory has been involved in research projects which were directed towards identifying the possible mechanisms responsible for the toxicity differences between vitamins D2 and D3 in rats. The present research project was designed to isolate and identify new metabolites of vitamin D2 from serum of rats which were fed toxic doses of vitamin D2. Hypervitaminosis D2 was induced in 30 rats by feeding each rat with 1000 nmol of vitamin D2/day x 14 days. The rats were sacrificed on the 15th day and obtained 180 ml of serum. The lipid extract of the serum was directly analyzed by a straight phase HPLC system. The various vitamin D2 metabolites were monitored by their ultraviolet (UV) absorbance at 254 nm. One of the UV absorbing peaks did not comigrate with any of the known vitamin D2 metabolites. This unknown metabolite peak was further purified by HPLC and was then subjected to UV absorption spectrophotometry and mass spectrometry. The structure assignment of the new metabolite was established to be 4,25-dihydroxyvitamin D2 [4,25(OH)2D2] by the techniques of UV absorption spectrophotometry and mass spectrometry and by the new metabolite's susceptibility to sodium metaperiodate oxidation. At present the biological activity of this unique 'A-ring' hydroxylated vitamin D2 metabolite is not known. As this new metabolite is isolated from the serum of rats intoxicated with vitamin D2, we speculate that 4,25(OH)2D2 may be playing an important role in the deactivation of vitamin D2.
Animals↗
In vitro cytotoxicity of 5-aminosubstituted 20(S)-camptothecins. Part 1.
A number of 5-aminosubstituted 20(S)-camptothecin analogues were prepared via semi-synthesis starting from 20(S)-camptothecin and 9-methoxy 20(S)-camptothecin. In vitro anti-cancer activity of these analogues was determined using 60 human tumor cell line assay. Although water solubility of most of these compounds was improved compared to 20(S)-camptothecin, their anti-cancer activity was considerably diminished. However, only smaller substituents such as methylamine or hydroxylamine as present in 8s and 8t, respectively, showed good activity with improved water solubility.
Antineoplastic Agents↗
Perspective on assessment of vitamin D nutrition.
Although routine fortification of milk and a few other dairy products has been successful in preventing rickets in children, its impact on preventing vitamin D depletion in adults is less than satisfactory. The prevalence of vitamin D depletion in the elderly is on the rise again and appears to be more common than is currently appreciated. Several groups of individuals are at risk of developing vitamin D depletion, and a significant minority of otherwise healthy individuals is vitamin D insufficient. Unrecognized vitamin D depletion leads to secondary hyperparathyroidism, accelerates cortical bone loss, and increases the risk of hip fractures. With the availability of techniques to assess vitamin D nutrition, it is probably cost effective to routinely measure 25-hydroxyvitamin D levels in individuals at the greatest risk and in patients with various metabolic bone diseases to prevent vitamin D depletion. Early recognition and prompt treatment of vitamin D depletion improves functional well being of the individual, reduces morbidity related to bone loss and fractures, and is associated with a highly favorable cost/benefit ratio.
Humans↗
Meta-analysis of calcium bioavailability: a comparison of calcium citrate with calcium carbonate.
OBJECTIVE: To perform a meta-analysis of data from available published trials comparing the bioavailability of calcium carbonate with that of calcium citrate. DATA SOURCES: The whole set was comprised of 15 studies involving 184 subjects who underwent measurement of calcium absorption from calcium carbonate and calcium citrate. Category A excluded four studies for lack of physiological relevance, use of a mixed preparation with low content of calcium carbonate, or wide variability in results. Category B was comprised of five studies (from Category A) involving 71 subjects who took calcium supplements on an empty stomach. Category C was comprised of six studies (from Category A) involving 65 subjects who took calcium preparations with meals. METHOD: The meta-analysis of calcium absorption data from calcium carbonate and calcium citrate, with calculation of effect size and 95% confidence intervals. RESULTS: Calcium absorption from calcium citrate was consistently significantly higher than that from calcium carbonate by 20.0% in the whole set, by 24.0% in Category A, by 27.2% on an empty stomach, and by 21.6% with meals. CONCLUSION: Calcium citrate is better absorbed than calcium carbonate by approximately 22% to 27%, either on an empty stomach or co-administered with meals.
Biological Availability↗
Dielectric and high-pressure investigations on a thermotropic cubic mesophase.
Optically isotropic cubic mesophases, which are commonly exhibited by lyotropic materials, have been observed in a few thermotropic liquid crystalline systems also. Although the first thermotropic cubic mesophase was reported about 40 years ago, its existence in diverse systems is only a recent finding. Moreover, the investigations on this mesophase have mainly concentrated on the structural aspects. While the effect of pressure has not been reported, only one dielectric measurement seems to have been carried out. In this paper we present the results of our dielectric and high pressure investigations on a compound exhibiting a thermotropic cubic mesophase. Two salient results are (i) a low frequency relaxation mode is observed with a large dielectric strength with appreciable changes across the columnar-cubic and cubic-smectic C transitions; and (ii) the cubic phase ceases to exist when the applied pressure exceeds about 400 bar.
Journal Article↗
Is vitamin D redundant in an aquatic habitat?
Certain fish are very rich sources of vitamin D as compared to most of the higher vertebrates which have insignificant amounts of this vitamin. Not only the teleosts, which possess a calcified skeleton, but also the elasmobranchs, which lack calcified skeleton, contain extremely high concentrations of this vitamin, leading to the speculation that the function of vitamin D in fish may be different from its known classical functions in terrestrial animals. Interestingly, the two most common calcemic hormones associated with Ca and P homeostasis in higher vertebrates are either missing [parathyroid hormone (PTH)] or inactive [calcitonin (CT)] in fish. In fact, these hormones appear to have developed after transition of life from water (Ca-P rich environment) to land (environment poor in Ca and P). Thus, living in an aquatic environment with a continuous rich supply of Ca and P, do fish need vitamin D? If so, does it need to be converted to its polar forms? Additionally what are the functions of vitamin D and its metabolites in fish? Since fish stand between the invertebrates and higher vertebrates in evolution, they serve as a unique model for the study of the evolutionary and physiological significance of vitamin D. Investigations have demonstrated that the source of a high amount of vitamin D in them is primarily through their food-chain (plankton). In addition, it appears from the studies in fish that vitamin D perhaps had no physiological function in the calcium-rich aquatic environment, and its metabolism was essentially for catabolic purposes. During the course of evolution, when life started on calcium poor terrestrial environment, vitamin D became functional and its metabolism, an anabolic one, was concerned with calcium homeostasis.
Animals↗
Vitamin D2 is not biologically active for Rora (Labeo rohita) as vitamin D3.
The present investigation was directed towards finding the relative biopotency of vitamin D3 and D2 in fish. The freshwater column feeder fish Labeo rohita (Rora) was used for the study. The feeding of Rora with graded levels of vitamin D2 (550, 1,100 and 1,650 i.u./kg diet) and vitamin D3 (1,100 and 1,650 i.u./kg diet) resulted in no behavioural or morphological changes in comparison with the group fed a vitamin D-deficient diet. Also, the growth rate, feed efficiency, mortality rate, carcass protein, total lipids, calcium and phosphorus were found to remain unaltered in the vitamin D-deficient fish and fish fed any form of the vitamin. Further, there is no difference in any of the above parameters between the different doses of vitamin D3 or vitamin D2. Thus, the results of this study indicate that both of the forms of vitamin D (D2 or D3) are not biologically active for Rora (Labeo rohita) as a representative of freshwater fish.
Animals↗
Vitamin D3 and its metabolites have no role in calcium and phosphorus metabolism in Tilapia mossambica.
The physiological function of vitamin D in fishes still remains uncertain. Earlier we observed no relationship between vitamin D3 content of several freshwater fishes and their calcemic/phosphatemic status and bone mineral content. In the present study the effects of vitamin D3 and its metabolites, 25-hydroxy vitamin D3 (25-OH-D3) and 1,25-dihydroxy vitamin D3 [1,25-(OH)2D3], administration on serum calcium-phosphorus levels, intestinal calcium absorption, whole-body calcium-phosphorus uptake, and gill calcium binding protein (CaBP) activity in the freshwater fish, Tilapia mossambica (Tilapia) was examined. It was observed that vitamin D3 and its metabolites could alter neither serum calcium-phosphorus levels nor intestinal calcium absorption and gill CaBP activity in fish at various doses. Further, the whole-body uptake of labelled calcium and phosphorus was also unaffected by vitamin D3/1,25-(OH)2D3 at different levels and/or at various lengths of time. Thus these studies indicate that unlike in terrestrial vertebrates, vitamin D3 or its metabolites are not needed for calcium-phosphorus homeostasis in fish.
Animals↗
Bone mineral density (BMD) in obesity effect of weight loss.
It is generally believed that bone mineral density (BMD) is increased in obese subjects, but the effect of weight loss on BMD has not been well studied. Therefore, we evaluated BMD among 11 obese women (mean age 45.5 +/- 14.2 years) before and after weight loss achieved by ingesting an 800 calorie diet for 12 weeks. BMD measurements were made at baseline, 6 months and 1 year intervals. Urinary hydroxyproline:creatinine (H:Cr), calcium:creatinine (Ca:Cr) ratios were measured as indices of bone turnover. Mean weight at baseline was 103.8 +/- 15.8 kg and decreased to 83.2 +/- 12.2 at six months and was 85.8 +/- 14.2 kg at one year. Total body, hip and lumbar spine BMD were 1.12 +/- 0.07, .87 +/- 0.11, and 1.02 +/- 0.12 gm/cm2, respectively. Total body BMD was significantly lower at 12 months compared to baseline. No significant change was observed in BMD of the lumbar spine. There was also a significant decrease in hip BMD at six months and 12 months compared to baseline. H:Cr and Ca:Cr ratios did not change over time. We conclude that weight loss achieved by VLCD is accompanied by a statistically significant change in BMD, but the BMD remained in the normal range.
Body Weight↗