Changes In Ca Levels Research Articles

Serum Calcium Levels in Adult Patients With Chronic Hypoparathyroidism Treated With rhPTH(1–84) Compared With a Historical Control Cohort

Adult patients (pts) with chronic hypoparathyroidism (HypoPT) have wide fluctuations in albumin-corrected serum calcium (Ca) measurements.1 This study assessed Ca levels over a 5-yr period in adult pts with chronic HypoPT treated with or without recombinant human parathyroid hormone (1–84), rhPTH(1–84). The rhPTH(1–84)-treated pt cohort was from NCT01297309 (RACE) and NCT01199614 (HEXT) clinical trials. A historical control pt cohort with chronic HypoPT who did not receive rhPTH(1–84) or rhPTH(1–34) came from the US Explorys electronic medical record database (Jan 2007−Aug 2019); selection criteria were similar to those used for the rhPTH(1–84)-treated cohort. The index date was the day after initiation of treatment for the rhPTH(1–84) cohort and the day after the first calcitriol prescription for the control cohort. Pts were required to have ≥1 pair of serum albumin and Ca values occurring on the same date during the 6 months before index and 5 yrs (±6 months) after index. For pts from RACE, baseline and study visit data after rhPTH(1–84) initiation were collected from the antecedent trials. Specified ranges for albumin-corrected serum Ca values were: <7.5 mg/dL (<1.875 mmol/L); ≥7.5−<8.0 mg/dL (≥1.875−<2.0 mmol/L); ≥8.0−<9.0 mg/dL (≥2.0−<2.25 mmol/L); ≥9.0−<10.2 mg/dL (≥2.25−<2.55 mmol/L); and ≥10.2 mg/dL (≥2.55 mmol/L). Changes in Ca levels were assessed using multivariable regression models. There were 71 pts in the rhPTH(1–84) cohort and 119 pts in the control. Before the index date, rhPTH(1–84)-treated pts, compared with the control, were younger (mean±SD, 47.8±10.8 vs 54.9±15.5 years; P<0.001) and a lower proportion had acute manifestations of HypoPT (22.5% vs 64.7%; P<0.001). Over a 5-yr period, in adjusted analyses rhPTH(1–84)-treated pts, compared with the control, had a similar mean proportion of <7.5 mg/dL Ca measurements per pt (13.1% vs 13.1%; P=0.41), a higher proportion of ≥7.5−<8.0 mg/dL Ca measurements per pt (18.8% vs 10.6%; P<0.001), a similar proportion of ≥8.0−<9.0 mg/dL Ca measurements per pt (50.7% vs 48.5%; P=0.68), a lower proportion of ≥9.0−<10.2 mg/dL Ca measurements per pt (15.6% vs 24.1%; P<0.001), and a lower proportion of ≥10.2 mg/dL Ca measurements per pt (1.9% vs 3.7%; P=0.27). The rhPTH(1–84) cohort, compared with the control, had a higher proportion of pts with target range Ca measurements ≥7.5−<9.0 mg/dL (≥1.875−<2.25 mmol/L) for at least 50% of their values (88.7% vs 62.2%; P<0.001). Data interpretation is limited by the differing pt management (ie, trial protocols for the rhPTH[1–84] cohort and clinical practice for the control cohort). Over a 5-yr period, per pt serum Ca levels fluctuated in pts with chronic HypoPT, but levels were more stable in pts treated with rhPTH(1–84) and a lower proportion had hypercalcemia, compared with controls. 1. Ayodele O, et al. ASBMR 2020, 11−15 Sep 2020.

The effects of rosuvastatin and pravastatin on bone metabolism in diabetic rats

Aim: In this study, the effects of rosuvastatin and pravastatin on bone metabolism were evaluated. Comparison of the positive or negative effects of two different statins on biochemical parameters related to bone metabolism in 20 mg / kg / day diabetic rats will be contribute to the enrichment of the literature on this subject. In addition, information will be obtained about whether the use of statins will be beneficial in bone metabolism disorders that may occur due to aging or diabetes in DM patients. Materials and Methods: In a diabetic rat model induced by Streptozotocin (STZ), the possible effects of Rosuvastatin and Pravastatin, both of which are hydrophilic, on biochemical parameters and histologycal examination related to bone metabolism (20 mg / kg) were examined in comparison with the control groups. Results: In the intergroup comparisons, Phosphate (P) level was lower in the Pravastatin group than the controls (P = 0.017). However, there was no difference in the P level in the Rosuvastatin group compared to the control group and the diabetes group. The calcium (Ca) level was increased in the Rosuvastatin group then the the controls (P = 0.002). However, there was no significant change in Ca level in the Pravastatin group. The vitamin D2 level of rats was similar in all groups and was not statistically significant. There was no significant difference between the groups in terms of both osteoblastic activity and bone marrow cellularity. Conclusion: In conclusion, although more extensive studies are needed, our study revealed that the serum Ca level was high in rats given rosuvastatin, and P levels were low in rats given pravastatin. But cytologically, there was no change in bone structure. Our study revealed that we should be a little more cautious about the information that statins have a positive effect on bone tissue.

Repeated Stress Exaggerates Lipopolysaccharide-Induced Inflammatory Response in the Rat Spleen.

Spleen is an immune organ innervated with sympathetic nerves which together with adrenomedullary system control splenic immune functions. However, the mechanism by which prior stress exposure modulates the immune response induced by immunogenic challenge is not sufficiently clarified. Thus, the aim of this study was to investigate the effect of asingle (2h) and repeated (2h daily for 7days) immobilization stress (IMO) on the innate immune response in the spleen induced by lipopolysaccharide (LPS, 100µg/kg). LPS elevated splenic levels of norepinephrine and epinephrine, while prior IMO prevented this response. LPS did not alter de novo production of catecholamines, however, prior IMO attenuated phenylethanolamine N-methyltransferase gene expression. Particularly repeated IMO exacerbated LPS-induced down-regulation of α1B- and β1-adrenergic receptors (ARs), while enhanced α2A- and β2-AR mRNAs. Elevated expression of inflammatory mediators (iNOS2, IL-1β, IL-6, TNF-α, IL-10) was observed following LPS and repeated IMO againpotentiated this effect. These changes were associated with enhanced Ly6C gene expression, a monocyte marker, and elevated MCP-1, GM-CSF, and CXCL1 mRNAs suggesting an increased recruitment of monocytes and neutrophils into the spleen. Additionally, we observed increased Bax/Bcl-1 mRNA ratio together with reduced B cell numbersin rats exposed to repeated IMOand treated with LPSbut not inacutely stressed rats. Altogether, these data indicate that repeated stress via changes in CA levels and specific α- and β-AR subtypes exaggerates the inflammatory response likely by recruiting peripheral monocytes and neutrophils to the spleen, resulting in the induction of apoptosis within this tissue, particularly in B cells. These changes may alter the splenic immune functions with potentially pathological consequences.

Efficacy of Continuous Oral Administration of Lanthanum Carbonate over 24 months

To examine the efficacy of long-term administration of lanthanum carbonate, changes in serum Ca, phosphate, whole parathyroid hormone (wPTH), and ALP were examined in 40 patients who were able to tolerate dosage of lanthanum carbonate over a continuous period of 24 months. Concurrently, concomitant administration of other phosphate binders, cinacalcet, vitamin D, etc., was also examined. After 24 months, serum phosphorus levels (P levels) had decreased to within management target of guidelines, from 6.16 ± 1.44 mg/dL to 5.58 ± 1.15 mg/dL, and this effect was maintained for 2 years. There were no changes in Ca level. wPTH did not change significantly but tended to increase at 12 months. The dose of concomitantly administered calcium carbonate and sevelamer hydrochloride was reduced. The P-lowering function of lanthanum carbonate still held steady at 24 months following the start of dosage. Because of the rising trend seen in wPTH, dose of cinacalcet and/or vitamin D need to be modulated. Reducing the number of concomitantly administered phosphate binder tablets was desirable from the standpoint of patient adherence.

Determination of Calcium and Iron in Prostate and Bladder Tumors by Atomic Absorption Spectrophotometer

Background and objective: Serum calcium and iron were used as a biochemical markers for investigation of the neoplastic diseases ,since there is a growing concern about the possible links between these minerals and tumors of various organs and tissues ,the objectives of this study were to determine the changes in the serum levels of Ca &amp; Fe ions in patients with benign prostatic hyperplasia and bladder cancer and to identify the role of these markers in diagnosis and prognosis of these patients . Methods: This study was done in Baghdad at Al-Kadhemia Teaching Hospital between 10/9/2002 and 1/9/2003 .Serum samples were obtained for measurement of calcium and iron.,which were determined by flame atomic absorption spectrophotometer . Results: Hypercalcemia affects up to 30% of patients with bladder and prostate cancers. In addition there were a decrease in the iron serum level as a result of tumor growth . Conclusion: Hypercalcemia, is one of the most common metabolic disorders accompanying neoplasia.The cancers most often associated with hypercalcemia, in addition there were a reduction in serum level of iron this biochemical marker may be associated with the pathogenesis of cancer.

Bone turnover and bone mineral density in type2 diabetes patients treated with rosiglitazone

Aim: The aim of our study was to investigate whether the administration of rosiglitazone affects bone metabolism and risk of fracture in patients with T2D. Methods: We have investigated 23 patients (9 males and 14 females) with T2D from age 38 to age 51. Patients were divided in two groups: in group I patients previously treated with diet alone were included, in group II — patients who received medications of sulfanilurea. Patients in both groups were prescribed to rosiglitazone 2 mg/d for 20 weeks. We measured HbA1c, fasting and postprandial glucose, ionized calcium (Ca), phosphorus values, parathyroid hormone (PTH), osteocalcin (OC). Bone mineral density was measured by dual-energy X-ray absorptiometry. Results: Rosiglitazone treatment was followed by decreased levels of OC (7.2±0.2 ng/ml, p<0.01). We have not revealed significant changes in bonemineral density in patients treatedwith rosiglitazone. There were no significant changes in levels of Ca (from 1.18± 0.01 mmol/l to 1.09±0.01 mmol/l) and PTH (from 38.3±0.01 pg/ml to 41.7±0.01 pg/ml). Conclusion: Rosiglitazone treatment was followed by decreased level of bone turnover. Conflict of interest: None declared.

Assessment of bone microarchitectural parameters and determination of fracture risk in humans with osteopenia; New results

Aim: The aim of our study was to investigate whether the administration of rosiglitazone affects bone metabolism and risk of fracture in patients with T2D. Methods: We have investigated 23 patients (9 males and 14 females) with T2D from age 38 to age 51. Patients were divided in two groups: in group I patients previously treated with diet alone were included, in group II — patients who received medications of sulfanilurea. Patients in both groups were prescribed to rosiglitazone 2 mg/d for 20 weeks. We measured HbA1c, fasting and postprandial glucose, ionized calcium (Ca), phosphorus values, parathyroid hormone (PTH), osteocalcin (OC). Bone mineral density was measured by dual-energy X-ray absorptiometry. Results: Rosiglitazone treatment was followed by decreased levels of OC (7.2±0.2 ng/ml, p<0.01). We have not revealed significant changes in bonemineral density in patients treatedwith rosiglitazone. There were no significant changes in levels of Ca (from 1.18± 0.01 mmol/l to 1.09±0.01 mmol/l) and PTH (from 38.3±0.01 pg/ml to 41.7±0.01 pg/ml). Conclusion: Rosiglitazone treatment was followed by decreased level of bone turnover. Conflict of interest: None declared.

Physiological and Histological Studies on Glucan as Modulator of Hazardous Effects in Rats Treated with Cyclophosphamide and Exposed to γ –Radiation

Aim of the work: -glucan which is known as biological response modifiers and immunostimulator was investigated in this study to minimize the toxicity of chemo-and radiotherapy induced by cyclophosphamide (CYP) and radiation exposure in rats. Materials and methods: -glucan was orally administered in a dose of 10 mg/kg b.wt. daily against the hazardous impacts of -irradiation (1 Gy daily up to 10 Gy) and/or CYP (50 mg/kg b.wt. every other day for 2 weeks). Determination of some biochemical analysis was carried out including calcium, alkaline phosphatase, creatine kinase, lactate dehydrogenase. Hematological analysis was performed on leucocytes and platelets counts. Additionally, histological study was also done on both lung and testis tissues. The experimental rats being sacrificed 1, 7 and 21 days post-treatment. Results: Treatment with CYP induced significant decrease in WBCs, platelets counts and alkaline phosphatase activity and significant increase of creatine kinase and LDH activities accompanied by a significant increase in Ca level only at the end of experimental period. Similar results were recorded with irradiated group accompanied with a non significant change in Ca level allover the experimental periods. Combined treatment with both -radiation and CYP intensified the effect of each other on most of the investigated parameters. Microscopic examination of the lung revealed that both γ-irradiation and CYP showed disturbed structure of bronchioles, thickened alveolar walls together with scattered haemorrhagic areas. Signs of pneumonia and compensatory emphysema were also seen. Meanwhile, in testis, irregular seminiferous tubules with reduction in their sizes were observed. Besides, the intertubular spaces were fibrotic and devoid of Leyding cells. Bizarre-shaped spermatogenic cells were also prominent. In combined treatment, these lesions became much more progressed. However, glucan administration prior to treatment with CYP or γ-radiation led to an improvement in most of biochemical, hematological and histological parameters under investigation. Conclusion: -glucan has a good protective role against the toxic effects associated with chemo-and radiotherapy.

Physiological and Histological Studies on Glucan as Modulator of Hazardous Effects in Rats Treated with Cyclophosphamide and Exposed to γ –Radiation

Aim of the work: -glucan which is known as biological response modifiers and immunostimulator was investigated in this study to minimize the toxicity of chemo-and radiotherapy induced by cyclophosphamide (CYP) and radiation exposure in rats. Materials and methods: -glucan was orally administered in a dose of 10 mg/kg b.wt. daily against the hazardous impacts of -irradiation (1 Gy daily up to 10 Gy) and/or CYP (50 mg/kg b.wt. every other day for 2 weeks). Determination of some biochemical analysis was carried out including calcium, alkaline phosphatase, creatine kinase, lactate dehydrogenase. Hematological analysis was performed on leucocytes and platelets counts. Additionally, histological study was also done on both lung and testis tissues. The experimental rats being sacrificed 1, 7 and 21 days post-treatment. Results: Treatment with CYP induced significant decrease in WBCs, platelets counts and alkaline phosphatase activity and significant increase of creatine kinase and LDH activities accompanied by a significant increase in Ca level only at the end of experimental period. Similar results were recorded with irradiated group accompanied with a non significant change in Ca level allover the experimental periods. Combined treatment with both -radiation and CYP intensified the effect of each other on most of the investigated parameters. Microscopic examination of the lung revealed that both γ-irradiation and CYP showed disturbed structure of bronchioles, thickened alveolar walls together with scattered haemorrhagic areas. Signs of pneumonia and compensatory emphysema were also seen. Meanwhile, in testis, irregular seminiferous tubules with reduction in their sizes were observed. Besides, the intertubular spaces were fibrotic and devoid of Leyding cells. Bizarre-shaped spermatogenic cells were also prominent. In combined treatment, these lesions became much more progressed. However, glucan administration prior to treatment with CYP or γ-radiation led to an improvement in most of biochemical, hematological and histological parameters under investigation. Conclusion: -glucan has a good protective role against the toxic effects associated with chemo-and radiotherapy.

A 32P-Postlabeling Assay for the Oxidative DNA Lesion 8,5′-Cyclo-2′-deoxyadenosine in Mammalian Tissues: EVIDENCE THAT FOUR TYPE II I-COMPOUNDS ARE DINUCLEOTIDES CONTAINING THE LESION IN THE 3′ NUCLEOTIDE

8,5'-Cyclopurine-2'-deoxynucleotides, which are strong blocks to mammalian DNA and RNA polymerases, represent a novel class of oxidative DNA lesion in that they are specifically repaired by nucleotide excision repair but not by base excision repair or direct enzymatic reversion. Previous studies using thin layer chromatography of (32)P-postlabeled DNA digests have detected several bulky oxidative lesions of unknown structure, called I-compounds, in DNA from normal mammalian organs. We investigated whether any of these type II I-compounds contained 8,5'-cyclo-2'-deoxyadenosine (cA). Two previously detected type II I-compounds were found to be dinucleotides of the sequence pAp-cAp and pCp-cAp. Furthermore, a modification of the technique resulted in detection of two additional I-compounds, pTp-cAp and pGp-cAp. Each I-compound isolated from neonatal rat liver DNA matched authentic (32)P-labeled cA-containing chromatographic standards under nine different chromatographic conditions. Their levels increased significantly after normal birth. The (32)P-postlabeling technique used here is capable of detecting 1-5 lesions/diploid mammalian cell. Thus, it should now be possible to detect changes of cA levels resulting from low level ionizing radiation and other conditions associated with oxidative stress, and to assess cA levels in tissues from patients with the genetic disease xeroderma pigmentosum who are unable to carry out nucleotide excision repair.

Calcium Signaling: Linking Environmental Signals to Cellular Functions

Topics discussed in this review include Ca in signal-response coupling and the specificity of Ca 2+ signals. It is concluded that Ca is the most important signalling molecule in plants. The source of Ca and the type of cell responding to a particular signal confers specificity at the primary level. At other levels, specificity is achieved by the strength of the Ca signal and the specific patterns of Ca change. Another level of control is achieved by changes in activity of various other proteins and factors that become activated or modulated by changes in Ca levels. Ca-dependent kinases and phosphatases belong to this category and are main components of signal response coupling. Changes in the level of other factors in concert with Ca also activate a specific set of proteins, and this could also be involved in contribution to the specificity of signalling. Ca directly affecting the expression of certain genes gives another level of control on specificity. Other components in the regulation of Ca signalling are also discussed.

What do CA 125 and other antigens tell us about ovarian cancer biology?

CA 125 is an antigenic determinant on a high molecular weight glycoprotein. A monoclonal antibody has been produced which recognizes this, and allows us to measure the expression of CA 125 in serum. Tissue distribution of the CA 125 determinant is most commonly seen in serous tumors of the ovary, with highest levels in borderline and frankly malignant serous cystadenocarcinomas. Occasionally cancers of the breast, gastrointestinal tract, and kidney will show elevated levels of CA 125. Normal tissues which show varying levels of CA 125 include decidual tissue and structures derived from celomic epithelium. CA 125 is clearly tumor associated, but not tumor specific. Quantitative correlation of CA 125 levels with tumor volume has not been demonstrated. This observation limits the clinical usefulness of CA 125 as a screening tool, particularly in premenopausal patients who do not have a diagnosis of ovarian cancer. An undetectable level of CA 125 antigen does not rule out the presence of an early ovarian cancer. When CA 125 is used to monitor disease state in patients with known ovarian cancers (whose tumors do express CA 125), changes in levels of CA 125 do correlate with gross changes in tumor volume. Good prognostic significance is attributed to a rapid decline in CA 125 levels following induction chemotherapy in patients with advanced ovarian cancer. However, an undetectable serum level of CA 125 does not predict clinical cure for a patient with ovarian cancer. Further clinical studies continue in the use of CA 125 as a screening tool and as a means to monitor treatment responses of known ovarian cancer.

Depolarization- and transmitter-induced changes in intracellular Ca2+ of rat cerebellar granule cells in explant cultures

Digital imaging of the Ca indicator fura-2 has been used to study the responses of developing granule cells in culture to depolarization and transmitter action. Unstimulated cells bathed in Krebs saline exhibited cytoplasmic Ca ion concentrations, [Ca2+], that were generally in the 30-60 nM range. Exposure of cells to high-potassium (25 mM) saline depolarized the membrane potential and produced an immediate rise in [Ca2+] that recovered within 2-3 min in normal saline. The response grew progressively larger over the first 20 d in culture. Transient increases in [Ca2+] to levels greater than 1 microM were observed after 12-14 d in vitro, at which time the cells displayed intense electrical activity when exposed to high K. At this stage, the increases were attenuated by blocking action potential activity with TTX. In TTX-treated or immature cells, in which the transient phase of the Ca change was relatively small, a second exposure to high K typically produced a much larger Ca response that the initial exposure. The duration of this facilitation of the response persisted for periods longer than 5 min. Application of the neurotransmitter GABA induced a transient increase in membrane conductance, with a reversal potential near resting potential (approx. -60 mV), and caused an intracellular Ca2+ increase that outlasted the exposure to GABA by several minutes. Glutamate, or kainate, induced an increase in membrane conductance but with a reversal potential more positive than spike threshold. These agents also elevated intracellular Ca2+, but unlike the case with GABA, this Ca response reversed rapidly upon removal of the transmitter. The facilitatory effect of repeated exposures to high-K saline, as well as the persistent Ca elevation following a brief GABA application, suggests that granule cells possess the capability of displaying activity-dependent changes in Ca levels in culture.

Calcium transport across the isolated dually perfused human placental lobule.

1. Movements of 45Ca and 3H2O in maternal to fetal (M----F) and fetal to maternal (F----M) directions across the dually perfused isolated human placental lobule were measured under steady-state conditions. 2. M----F values of the clearances (CR) and extractions (ER) of 45Ca relative to 3H2O were 0.371 +/- 0.056 and 0.492 +/- 0.086 (mean +/- S.E. of mean) respectively. The corresponding values for F----M movements were 0.277 +/- 0.017 and 0.251 +/- 0.010 respectively. The F----M perfusion flow ratio (QF/QM) was 0.34 +/- 0.01 throughout. Comparison with previously published data indicated a significant degree of membrane limitation to Ca transfers. 3. There was evidence of a mismatch between tissues receiving a fetal and those receiving a maternal perfusion. 4. The relative extraction ER was markedly and reversibly enhanced when perfusate total Ca was reduced from 2.4 to 0.1 mM. The effect was present in both M----F and F----M transfers and provided evidence for carrier-mediated uptake of Ca on both aspects of the placental barrier. Small and transient decreases in the relative clearance CR were observed on changing from 2.4 to 0.1 mM-Ca in M----F and to a lesser extent F----M transfers while transient increases were seen on changing from 0.1 back to 2.4 mM-Ca. 5. Measurement of net changes in Ca levels in closed-circuit studies indicated a significant release of both ionized (Ca2+) and total (CaT) Ca into the fetal perfusate at total Ringer solution concentrations of 1.4, 1.9 and 2.4 mM-Ca. Release of Ca into the maternal circuit was also observed using 1.4 mM-Ca Ringer solution but when 1.9 and 2.4 mM-Ca Ringer solution was used a net uptake occurred. 6. These findings strongly suggest that mechanisms by which Ca is transferred from M----F circulations in vivo are at least partly preserved in the in vitro human placental preparation. They indicate that this preparation is suitable for the study of these mechanisms and their regulation by hormonal and other factors.

Drug-induced changes in monoamine levels in the sympathetic adrenergic ganglion cells and terminals. A histochemical study.

AbstractNorberg, K.‐A. Drug‐induced changes in monoamine levels in the sympathetic adrenergic ganglion cells and terminals. A histochemical study. Acta physiol. scand. 1965. 65, 221–234.— The cell bodies of peripheral adrenergic neurons in rat sympathetic ganglia have been studied and compared with the adrenergic nerve terminals in respect of drug‐induced changes in CA levels and uptake‐accumulation of CA, DOPA and 5‐HTP, using the histochemical fluorescence method of Falck and Hillarp. The cell bodies show about the same rapid depletion as the terminals following the administration of reserpine and a‐MMT but recover much more quickly. After m‐tyrosine, depletion and recovery occur rapidly and simultaneously in both parts of the neuron. The findings are in accordance with the view that the transmitter granules are formed in the cell bodies. The increased NA content observed in the superior cervical ganglion following the administration of MAO inhibitors was found to be localized predominantly to the cell bodies of the adrenergic neuron. The cells react largely as two different populations: one showing a more or less pronounced amine increase, the other no or only a slight increase. — An accumulation of CA is found in the adrenergic neuron but not in other types of peripheral neurons following the administration of DA, NA or L‐DOPA. The efficient reserpine‐insensitive mechanism for the uptake‐concentration of NA that is localized to the level of the cell membrane of the adrenergic axons and terminals (Hamberger et al. 1964, Malmfors 1965) is present also in the cell bodies. — As regards the uptake or possibly decarboxylation of DOPA and 5‐HTP, the adrenergic neuron shows a marked specificity for DOPA. — The experiments show that the cell bodies and terminals have qualitatively the same properties.