Abstract  The synthesis and structure-activity relationship (SAR) of thiophene-C-glucosides have been explored, and the human sodium-dependent glucose cotransporter 2 (hSGLT2) inhibitory activities and rat urinary glucose excretion (UGE) effects of 3a-f were evaluated. As a result, they showed good hSGLT2 inhibitory activities and rat UGE effects. In particular, the chlorothiophene derivative 3f showed remarkable inhibitory activity against hSGLT2.

Abstract  Applicability of a skin test induced by dinitrofluorobenzene [DNFB] to quantification of the actual level of cellular immunity [CI] in vivo and its level after an experimental immunomodulation intervention were evaluated in two breeds [40 animals in each] of fattening bulls [10-11 months old]. At the selected methodical procedure of intensity determination of the delayed type of hypersensitivity [DTH], its average value reached 4.5 + 1.5 mm in 80 animals, while in 77.5 % of bulls its level ranged from 3.6 to 9.6 mm. in 18.7 % from 2.0 to 3.5 mm and in 3.8 % remained less than 2.0 mm Evident expression of the reaction points to the possibility of application of the used methodical procedure of the skin test using DNFB to quantify the level of CI response in vivo in cattle. Percentual representation of animals according to the intensity of skin reaction [Tab. I] and concentration of total serum immunoglobulins [CS-Ig] and serum IgG [Tab. II] indicates the different cellular and humoral state of animals in investigated breeds. This is also confirmed by the recorded average values of mentioned parameters which were significantly lower [P < 0.01; or 0.05] In animals of the first breed [4.0 +/- 1.3 mm; 28.3 +/- 4.4 U ZST, 18.4 +/- 3.5 g . l-1] than in breed 2 [4.9 +/- 1.6 mm: 32.5 +/- 3.8 U ZST; 20.3 +/- 3.5 g . l-1]. The animals of each breed were divided into four experimental groups with the approximately equal actual levels of DTH [Tab. III]. Immunomodulation effects of a single administration of soluble fungal glucal [Pleurotus ostreatus] at the dose 5 mg [RFG 5 group] and 10 mg . kg-1 [RFG 10 group] and levamisol [Nilverm inj.] at the dose 5 mg . kg-1 [L 5 group] on CI response tested on day 30 after application were compared to the control. While animals of breed 1 demonstrated positive glucal effects. for both doses used on DTH reaction to DNFB, both in comparison to its level before application [P < 0.5] and to the level of control animals after its application [P < 0.05; or 0.01], [Tab. III]. similar effects of glucan were recorded in the bulls of breed 2 no. Potentiating effects of levamisol [5 mg . kg-1] on DTH to DNFB were observed in none of the breeds.

Abstract  The effect of an intravenous calcium gluconate load (10 mg/kg over 5 min) on plasma ionized calcium concentration, parathyroid hormone (PTH), and the rate of urinary excretion of calcium, sodium, and nephrogenous cyclic adenosine monophosphate (NcAMP) was examined in 26 patients with essential hypertension and 27 age- and sex-matched normotensive subjects. Prior to calcium administration hypertensives had lower plasma ionized calcium concentration (P < .01) and higher PTH levels (P < .001) and excreted more calcium (P < .05) and NcAMP (P < .001) in the urine compared to normotensives. Following calcium infusion, plasma ionized calcium did not differ significantly between the two groups, but PTH levels remained higher in the hypertensive subjects at both 60 min (P < .001), and at 120 min (P = .02) post-load. Post-load values for both urinary calcium excretion and urinary sodium excretion were significantly higher in the hypertensive subjects than in the control group. Both before and after calcium infusion, urinary calcium excretion was positively correlated with urinary sodium excretion in each of the two groups, but for the same level of sodium excretion, hypertensives excreted more calcium in the urine, compared to normotensives, both before (P < .05) and after calcium infusion (P < .001). A positive correlation between basal plasma renin activity (PRA) values and plasma ionized calcium values obtained before (r = 0.42, P = .03) or at 60 min (r = 0.41, P = .03) and 120 min (r = 0.42, P = .03) after calcium infusion existed only in the hypertensive subject group. Post-load urinary sodium excretion values were negatively correlated to basal PRA values in both groups (r = -0.55, P < .01 and r = -0.58, P < .01 for hypertensives and normotensives, respectively), but a similar negative correlation between post-load urinary calcium excretion values and basal PRA values existed only in the hypertensive subject group (r = -0.50, P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract  20 hemodialysis patients (age xBAR = 58.9 +/- 14.8 years, 10 male patients, dialysis since xBAR = 45.9 +/- 39.4 months) with more than six months lasting hyperphosphatemia and serum-phosphate levels higher than 2 mmol/l, wich was refractory to usual phosphate binding therapy, were selected from our 217 ambulatory hemodialysis patients. The chronic treatment with calcium gluconate, calcium carbonate or aluminiumhydroxide was changed to calcium acetate (CA), using identical numbers of tablets (xBAR = 5.6 tabl./day: containing 616 mg elementary calcium). During 4 months of treatment. CA was prescribed in the 2nd and 4th month, the former phosphate binders in the 1st and 3rd. Under the administration of Ca, there was a decrease of S-phosphate levels in comparison with the former phosphate binders (2.15 +/- 0.37 versus 2.29 +/- 0.32 mmol/l), the calcium-phosphate product was slightly ameliorated 15.18 +/- 0,88 versus 5.49 +/- 0.76 mmol/l). calcium concentration (2.42 +/- 0.15 versus 2,40 +/- 0.15 mmol/l). standard bicarbonate and serum pH did not change. As a new phosphate binder, CA was superior to Ca-gluconate, and, in single cases, more effective than Ca-carbonate and even aluminumhydroxide. In conclusion, patients with poor compliance and severe hyperphosphatemia may benefit from treatment with calcium acetate.

Abstract  The solid dispersion technique is one of the most effective methods for improving the dissolution rate of poorly water-soluble drugs; however this is reliant on a suitable carrier and solvent being selected. The work presented explores amino sugars (d-glucosamine HCl and d-gluconolactone) as potential hydrophilic carriers to improve dissolution rate of a poorly water-soluble drug, piroxicam, from physical mixtures and solid dispersion formulations. Solid dispersions of the drug and carrier were prepared using different ratios by the conventional solvent evaporation method. Acetone was used as solvent in the preparation of solid dispersions. Physical mixtures of piroxicam and carrier were also prepared for comparison. The properties of all solid dispersions and physical mixtures were studied using a dissolution tester, Fourier transform infrared, XRD, SEM and differential scanning calorimetry. These results showed that the presence of glucosamine or gluconolactone can increase dissolution rate of piroxicam compared to pure piroxicam. Glucosamine or Gluconolactone could be used as carrier in solid dispersion formulations and physical mixtures to enhance the dissolution rate. Solid state studies showed that no significant changes occurred for piroxicam in physical mixtures and solid dispersion.

Abstract  Context. This is the first case of proton pump induced hypomagnesemia and hypocalcemia, accompanied with increased parathormone levels.

Objective. The proton pump inhibitors are widely used medications. They are considered safe, however, they have some side effects. One of these side effects is hypomagnesemia. Here we report a case with severe hypocalcemia and hypomagnesemia due to long term proton pump inhibitor.

Case. A 73 years old woman, admitted to emergency room due to generalized tonic-clonic seizures. She had a previous history of muscle cramps and paresthesia for 4 months. She had a medical history of peptic ulcer and she was taking omeprazole for 7 years. Her laboratory evaluation showed marked hypomagnesemia [0.5 mg/dL (normal: 1.7-2.55 mg/dL)] and hypocalcemia [6.2 mg/dL (8.8-10.2 mg/dL)] with extremely low urinary calcium (Ca) and magnesium (Mg) excretion [0.01 gr/24 h (normal:0.05-0.3 gr/24 h), <1.22 mg/24 h (normal: 9.7-12.20) respectively]. Her vitamin D level was normal [35 ng/mL (normal:30-80 ng/mL)] and PTH was increased [129 pg/mL (normal: 15-65 pg/mL)] in accordance with the secondary hyperparathyroidism. Symptoms resolved with the intravenous supplementation of calcium gluconate and magnesium sulphate. However, despite high levels of oral replacement, Mg levels remained low. With omission of omeprazole two months after the admission, her ion levels returned to normal without any replacement.

Conclusion. Especially elderly patients with long term proton pump inhibitor therapy, should be monitored for the symptoms of hypocalcemia and hypomagnesemia.

Abstract  A 3 4/12-year-old boy with normal renal function was seen for chronic constipation and treated with an adult-size phosphate enema. Shortly afterwards, he became somnolent and developed severe hyperphosphatemia with hypocalcemia and tetany, hypernatremia and metabolic acidosis. Intravenous fluids and calcium gluconate were given; tetany disappeared rapidly, the mental status improved and most serum electrolytes normalized within one day. This report demonstrates that phosphate enemas are not only inappropriate for small children, they are outright dangerous.

Abstract  Reactions to human serum albumin (HSA) in therapeutic plasma exchange (TPE) are rare. Nevertheless, older literature describes possible adverse effects, including specific immune responses to albumin or other proteins, and reactions due to contaminating organisms or pyrogen. During an eight day period three patients in our unit had unusual reactions after infusion of 1.5-2 L of HSA. Patient 1 had trembling that persisted for 20 min. Patient 2 had shaking for 40 min despite calcium gluconate infusion, and fever to 100.8 degrees F. Patient 3 had severe rigors that subsided after 90 min when meperidine was finally given, and fever to 103.5 degrees F. Record reviews revealed that all three patients had received HSA from the same lot, and that only one other TPE patient had received HSA from that lot. Neither our pharmacy nor the manufacturer was aware of other reactions associated with that lot. Material from a bottle only partially infused to patient 3 was negative in culture and was negative far pyrogen when retested by the manufacturer. Nevertheless, because patients 1 and 2 had each had multiple previous uneventful TPEs and because all three patients tolerated subsequent TPEs without incident when another brand of HSA was used, we conclude that these patients had pyrogen reactions to the implicated HSA lot. This experience illustrates the value of cluster recognition in arousing suspicion of unusual reactions to HSA and the value of recorded lot numbers in pursuing such suspicions. Apheresis personnel should be aware of the potential for pyrogen reactions with HSA and should record lot numbers of all fluids infused during TPE. (C) 1995 Wiley-Liss, Inc.

Abstract  Introduction. Hydrofluoric acid is a fluoride-substituted compound used in the chemical industry. Burns and hypocalcaemia result from ingestion or contact with the skin or mucosal membranes. We observed burns and skin necrosis on the hands after home use of low-concentration hydrofluoric acid.

Case report. A 57-year-old woman consulted in February 1994 for oedema, erythema and very painful burns of the palms of both hands. The day before, she had used a home-made furniture cleanser containing 5 p. 100 hydrofluoric acid. At admission, cal calcium and radiography of the two hands were normal. She was given a topical application of 5 p. 100 calcium chloride. The clinical course was favourable with squamation of both palms then necrotic lesions of the pulp on the 1 st, 2 nd and 3 rd fingers. Discussion. Such exposure in a household situation is unusual. Hydrofluoric acid has two dangerous mechanisms of action. First it is a caustic substance producing late-onset burns and secondly hypocalcaemia results from precipitation of insoluble calcium fluoride. The risk of hypocalcaemia is greatest when a large aera of the skin is exposed. Prognosis depends on early treatment based on prevention of hypocalcaemia by abundant washing of the teguments and permanent application of a 5 p. 100 calcium gluconate solution associated with local skin treatments. Careful follow-up is required with regular calcium chemistries.

Abstract  1. Experiments were conducted to test for the presence of basolateral Na+ channels in the rat lingual epithelium. Researchers have proposed a model in which some lingual taste cells have Na+ channels in the basolateral membrane. That model is designed to account for the portion of the neural taste response and the portion of the transepithelial short-circuit current (I-sc) in vitro that are insensitive to mucosal amiloride; some Na+ would diffuse across the tight junction into the cell via this lateral pathway, and would be transported out of the cell by Na+ pumps in the basal membrane. The model could also account for the differential effect of mucosal amiloride on Na+ salts of various anions, in which the neural taste responses to Na+ salts with anions larger than Cl- are more sensitive to mucosal amiloride than is the taste response to NaCl.

2. Voltage-clamp data were obtained from an in vitro preparation of the anterior-dorsal rat tongue epithelium in which the connective tissue was removed by enzyme digestion. I-sc in a modified Ussing chamber was reduced by amiloride in the submucosal solution.

3. The pattern of sensitivity to submucosal amiloride differed in several respects from the pattern for mucosal amiloride. The inhibition constant (K-1) was 52 mu M amiloride concentration, higher than for the apical amiloride-sensitive Na+ channel. The selectivity for Na+ over K+ was much less than for the response to mucosal amiloride; with 0.5 M NaCl or KCI on the mucosal side, the ratio of inhibition for the NaCl response to inhibition for the KCl response varied between 1 and 3.

4. As the concentration of NaCl in the mucosal solution was varied, submucosal amiloride caused little inhibition of I-sc for mucosal NaCl below isosmotic concentration, with the percent inhibi tion increasing as mucosal salt concentration increased. With 0.5 M sodium gluconate in the mucosal solution, there was very little inhibition due to submucosal amiloride.

5. The results support the presence of amiloride-sensitive Na+ channels in the basolateral membranes of the dorsal tongue epithelium in rat, and are consistent with the proposed model in which these channels are present in taste cells.

Abstract  Delivery systems prepared with natural biopolymers are of particular interests for applications in food, pharmaceutics and biomedicine. In this study, nanocomplex particles of sodium caseinate (NaCas) and pectin were fabricated and investigated as potential oral delivery vehicles. Nanocomplexes were prepared with three mass ratios of NaCas/pectin by acidification using glucono-δ-lactone and thermal treatment. NaCas/pectin at 1:1 mass ratio resulted in dispersions with the lowest turbidity and the smallest and most uniform nanocomplexes. Thermal treatment at 85 °C for 30 min facilitated the formation of stable, compact, and spherical nanocomplexes. Heating not only greatly increased the yield of nanocomplexes but also significantly improved the encapsulation capability of rutin studied as a model compound. Pectin in nanocomplexes delayed the hydrolysis of NaCas by pepsin at gastric conditions and enabled the controlled release of most rutin in simulated intestinal conditions. The nanocomplexes based on food-sourced biopolymers have promising features for oral delivery of nutrients and medicines.

Abstract  BACKGROUND: A new protocol for the Amicus separator (Fresenius Kabi) enables the device to perform plasma exchange (PE). The aim of the study was to compare retrospectively the plasma removal efficiency (PRE) of the Amicus, the Optia (TerumoBCT), and the Spectra (TerumoBCT) when performing PEs.

STUDY DESIGN AND METHODS: We retrospectively reviewed patients who received at least one PE with the Amicus and at least one PE with the Optia, the Spectra, or both. We collected data regarding PRE, volume of anticoagulant and calcium-magnesium (Ca-Mg) solution infused, and changes in laboratory data from patients' blood sampled immediately before starting and immediately after finishing each PE procedure: complete blood count, coagulation, acid-base equilibrium, and biochemistry variables. We also collected severe adverse events (AEs).

RESULTS: We performed 18, 44, and 14 PEs with the Amicus, Optia, and Spectra, respectively. We observed significant differences among the Amicus, Optia, and Spectra regarding PRE (79.8 ± 8.2, 82.9 ± 5.8, and 70.4 ± 8.2%; p < 0.001), volume of anticoagulant infused (542 ± 196, 687 ± 120, and 647 ± 111 mL; p = 0.002), volume of Ca-Mg solution infused (81 ± 28, 56 ± 16, and 63 ± 15 mL; p < 0.001), absolute change of ionic Ca (-0.04 ± 0.13, -0.05 ± 0.12, and -0.19 ± 0.16 mmol/L; p = 0.002), and absolute change of Na (1.18 ± 1.97, 1.02 ± 1.93, and 3.71 ± 1.98 mEq/L; p < 0.001). We observed no significant differences in other analytic variables and we observed no severe AEs.

CONCLUSION: The Amicus device could effectively perform PE procedures. In terms of PRE, the Amicus and Optia were similar, but both devices were superior to the Spectra. The Amicus used a lower volume of anticoagulant when compared with the Optia.

Abstract  Triple recycling (i.e., enterohepatic, enteric and local recycling) plays a central role in governing the disposition of phenolics such as flavonoids, resulting in low systemic bioavailability but higher gut bioavailability and longer than expected apparent half-life. The present study aims to investigate the coexistence of these recycling schemes using model bioactive flavonoid tilianin and a four-site perfused rat intestinal model in the presence or absence of a lactase phlorizin hydrolase (LPH) inhibitor gluconolactone and/or a glucuronidase inhibitor saccharolactone. The result showed that tilianin could be metabolized into tilianin glucuronide, acacetin, and acacetin glucuronide, which are excreted into the bile and luminal perfusate (highest in the duodenum and lowest in the colon). Gluconolactone (20 mM) significantly reduced the absorption of tilianin and the enteric and biliary excretion of acacetin glucuronide. Saccharolactone (0.1 mM) alone or in combination of gluconolactone also remarkably reduced the biliary and intestinal excretion of acacetin glucuronide. Acacetin glucuronides from bile or perfusate were rapidly hydrolyzed by bacterial β-glucuronidases to acacetin, enabling enterohepatic and enteric recycling. Moreover, saccharolactone-sensitive tilianin disposition and glucuronide deconjugation, which was more active in the small intestine than the colon, points to the small intestinal origin of the deconjugation enzyme and supports the presence of local recycling scheme. In conclusion, our studies have demonstrated triple recycling of a bioactive phenolic (i.e., a model flavonoid), and this recycling may have an impact on the site and duration of polyphenols pharmacokinetics in vivo.

Abstract  Recurrent renal stones associated with urinary infection were treated in eight kidneys in six patients by percutaneous nephrostomy and irrigation with hemiacidrin, a commercially available solution of organic acids and magnesium. The stones, presumably composed of triple phosphates (magnesium, ammonium and calcium phosphate), were completely dissolved in six kidneys; in two they were partially dissolved and subsequently recovered by other methods. No serious complications were encountered. The technic requires special precautions against perinephric and intravascular dissemination of infection, but it offers potentially effective therapy for certain kidney stones without the use of general anesthesia or operation.

Abstract  A previously healthy girl, without heart disease, who ingested 2400 mg of verapamil developed hypotension, trifasicular block pattern, mental confusion, mild metabolic acidosis, and hyperglycemia. She recovered with symptomatic and supportive therapy. A discussion is presented about the action mechanism of the drug.

Abstract  A quantitative method for calcium pangamate (Vitamin B15) and calcium gluconate determination, separately and in mixture, is proposed on the basis of the ferric hydroxamate procedure. The method may also be applied to the determination separately and in mixture, is proposed on the basis of the ferric of both preparations in mixture with various other substances which are not converted into lactone from in acid medium, and which the ferric hydroxamate procedure fails to develop.

Abstract  Calcium gluconate is irritating to soft tissues and can produce tissue necrosis and slough; Radiographs of the part following extravasation initially show only soft tissue swelling. A variable pattern of soft tissue calcification then develops in one to three weeks, and gradually is completely resorbed over several months' time. The cause of the soft tissue calcifications may be quite puzzling, if the incident of calcium gluconate extravasation has been overlooked.

Abstract  Changes in serum and tissue and urinary levels of fluoride, calcium and other biochemical consequences were investigated in rats after experimental hydrofluoric acid (HF) burns, to obtain adequate method of emergency treatment for the injury. Increases in ionized fluoride and decreases in total and ionized calcium, in the sera were observed after contact with HF. Hyponatremia and hyperkalemia were observed over a 24 hour period. Parathyroid hormone (PTH) concentrations were elevated in the sera taken within 24 hours after burn and fell to reference range once the calcium concentration had been raised. Electrocardiographic changes including severe bradycardia were observed. These results indicate that an HF skin burn results in systemic fluoride poisoning followed by hypocalcemia, hypersecretion of PTH, hyponatremia, hyperkalemia and other electrolytes imbalance. Flushing with running water was effective for HF burns. By applying 2.5% calcium gluconate jelly, concentrations of fluoride in the urine and the tissues surrounding the injured region were reduced. Thus, the present results proved that the irrigation with running water and the jelly applications was evaluated as the most effective therapy among various methods tested for the HF burn.

Abstract  We noted the presence of elevated levels of circulating 1,25-dihydroxyvitamin D (83 pg/ml (200 pmol/L), with low total serum calcium concentration (6.5 mg/dl (1.88 mmol/L), in an untreated adolescent boy with hypoparathyroidism. Furthermore, an inverse relationship between total serum calcium and circulating 1,25-dihydroxyvitamin D levels was evident during treatment with 1,25-dihydroxyvitamin D3. We examined this relationship with a 33-hour intravenous infusion of calcium gluconate in the absence of exogenous 1,25-dihydroxyvitamin D3 therapy. The infusion was accompanied by a gradual increase of both total serum calcium and blood ionized calcium concentrations from hypocalcemic to normocalcemic ranges, and produced a 50% reduction in circulating 1,25-dihydroxyvitamin D values, with minimal changes in circulating phosphorus, magnesium, and 25-hydroxyvitamin D values. These results suggest that calcium-dependent, parathyroid hormone-independent regulation of 1,25-dihydroxyvitamin D production may exist in human beings.