Predictions of Serum Phosphate Concentration during Continuous Renal Replacement Therapy Using a Steady-State Mass Balance Model.

INTRODUCTION: Hypophosphatemia is common during continuous renal replacement therapy (CRRT), but serum phosphate levels can potentially be maintained during treatment by either intravenous phosphate supplementation or addition of phosphate to renal replacement therapy (RRT) solutions. METHODS: We developed a steady-state phosphate mass balance model to assess the effects of CRRT dose on serum phosphate concentration when using both phosphate-free and phosphate-containing RRT solutions, with emphasis on low CRRT doses. RESULTS: The model predicted that measurements of serum phosphate concentration prior to (initial) and during CRRT (final) together with clinical data on CRRT dose, treatment duration, and phosphate supplementation can determine model patient parameters, that is, both the initial generation rate and clearance of phosphate prior to CRRT. Model parameters were then calculated from average patient data reported in several previous publications with a standard or high CRRT dose. Using representative model parameters for typical patients, predictions were then made of the effect of low CRRT dose on the change in serum phosphate levels after implementation of CRRT. The model predicted that CRRT at a low dose using phosphate-free RRT solutions will limit, but not eliminate, the incidence of hypophosphatemia. Further, the model predicted that CRRT at a low dose will have virtually no influence on the incidence of hyperphosphatemia when using phosphate-containing RRT solutions. CONCLUSIONS: This report identifies the clinical measurements to be used with the proposed model for individualizing the CRRT dose and RRT phosphate concentration to maintain serum phosphate concentrations in a desired range.

A prospective observational study of the use of desflurane anesthesia in Indian adult inpatients undergoing surgery: The Registry in India on Suprane Emergence registry.

BACKGROUND AND AIMS: Limited registry studies are available on the use of anesthetic agents. This registry was conducted to evaluate emergence outcomes in Indian adult patients undergoing surgery with desflurane anesthesia. MATERIAL AND METHODS: This multicenter, prospective, non-interventional, observational study (Registry in India on Suprane Emergence [RISE] registry) included adult inpatients who received desflurane as general anesthetic for surgical procedure of ≥2 h. Patients were stratified by age into three groups: ≥18-40 years, ≥41-65 years, and >65 years. Data on patients' demographics, practice, and usage pattern of medications were collected. The primary efficacy outcomes were time to extubation, time to response to verbal command, and time to orientation. RESULTS: Of 236 patients screened, 201 (≥18-40 years, n = 70; ≥41-65 years, n = 65; >65 years, n = 66) were enrolled in the study. Mean time to extubation observed in ≥18-40 years group was 7.2 ± 4.1 min, ≥41-65 years was 11.6 ± 8.99 min, and >65 years was 12.0 ± 10.5 min. Mean time to response to verbal command was 7.4 ± 4.3 min for ≥18-40 years, 10.9 ± 8.5 min for ≥41-65 years, and 10.0 ± 5.4 min for >65 years. Mean time to orientation was 13.0 ± 7.0 min for ≥18-40 years, 16.1 ± 12.0 min for ≥41-65 years, and 17.0 ± 8.6 min for >65 years. Incidence of nausea and retching/vomiting was observed in 8% of patients each in the postoperative period, and these complications were seen more in the >65 years age group. Overall, desflurane treatment maintained hemodynamic stability and no major airway events were reported. CONCLUSIONS: The RISE registry data suggest that desflurane-based anesthesia provides early recovery with stable hemodynamics without any airway adverse events, in a wide variety of surgical procedures.

Diacerein as adjuvant to diclofenac sodium in osteoarthritis knee.

AIM: To evaluate clinical effectiveness of diacerein as an adjuvant to diclofenac sodium in treatment of Indian patients with symptomatic osteoarthritis (OA) knee. METHODS: This is a prospective, double-blind, placebo-controlled and intention-to-treat study. An initial washout period of 1 week, was followed by 3 months treatment period during which patients were randomly divided to receive either capsule diacerein 50 mg or matched placebo once daily for the first month and twice daily for the next 2 months with diclofenac sodium 75 mg sustained release tablet once daily given to both groups. Patients were observed for one more month, using paracetamol as rescue therapy. Treatment efficacy was assessed by a visual analogue scale (VAS) and the Western Ontario and McMaster University (WOMAC) Osteoarthritis Index, patient and physician global assessment of OA, daily paracetamol intake. RESULTS: Of 84 patients screened, 74 patients formed the intent-to-treat population (37 patients in each group). At baseline, both groups were comparable and at the third month functional index and pain intensity were better in the diacerein group (VAS 15.33 ± 5.07; WOMAC 15.9 ± 2.40) as compared to the placebo group (VAS 22.83 ± 6.90;WOMAC 36.8 ± 2.92; P < 0.05). When analyzed at the fourth month, improvement persisted in the iacerein group (VAS 14.83 ± 5.16; WOMAC 16 ± 2.5) as compared to placebo group (VAS 33 ± 7.72; WOMAC 48.26 ± 3.5; P < 0.05), demonstrating the carry-over effect of diacerein, which was confirmed by lesser paracetamol consumption in the diacerein group (5.967 ± 0.8087) as compared to the placebo group (12.433 ± 2.128; P < 0.05). CONCLUSION: Use of diacerein and diclofenac sodium together decreases pain and improves joint function significantly more than diclofenac alone in OA knee.

Anti-insect potential of lectins from Arisaema species towards Bactrocera cucurbitae.

Bactrocera cucurbitae (Coquillett), also known as melon fruit fly, is one of the major insect pests of cucurbits in several parts of Asia, Africa and Pacific. In the present investigation, effect of lectins from two sources i.e. Arisaema intermedium Blume and Arisaema wallichianum Hook f. (Family-Araceae) has been studied on the development of second instar larvae of melon fruit fly. The lectins were incorporated separately in artificial diet at a concentration of 10 to 160 microg ml(-1) and fed adlibitum to the second instar larvae. Both the lectins were found to prolong the development period and significantly inhibited the pupation and emergence in a dose dependent manner. Total development period was found to be prolonged by 3.5 and 2.3 days in case of larvae fed on artificial diet containing A. intermedium (AIL) and A. wallichianum (AWL), respectively. LC50 values calculated on the basis of adult emergence came out to be 32.8 and 29 microg ml(-1) for AIL and AWL, respectively. Both the lectins tested, were found to increase the activity of esterases as larvae proceeded from 24 to 72 hr of treatment. The activity of acid phosphatase decreased significantly in larvae reared on diet containing LC50 of AIL, while in case of AWL significant decrease was observed only at 72 hr of treatment. Alkaline phosphatase activity decreased significantly on treatment with both of these lectins. These results showed that AIL and AWL have promising anti-insect potential. So, lectin gene/s from either of these species can be cloned and subsequently can be employed to develop transgenics to control melon fruit flies specifically and insect pests in general. This approach could be used as a part of Integrated pest management (IPM) strategies.

Effects of indian coral tree, Erythrina indica lectin on eggs and larval development of melon fruit fly, Bactrocera cucurbitae.

Present study was undertaken to investigate the influence of D-galactose binding lectin from Erythrina indica Lam. on the eggs and second instar larvae (64-72 hr) of melon fruit fly, Bactrocera cucurbitae (Coquillett). The lectin from E. indica seeds was extracted and purified by affinity chromatography using asilofetuin linked porous amino activated silica beads. The effects of various concentrations (0, 125, 250, 500 and 1000 microg ml(-1)) of lectin were studied on freshly laid eggs (0-8 hr) of B. cucurbitae which showed non-significant reduction in percent hatching of eggs. However, the treatment of second instar larvae (64-72 hr) with various test concentrations (0, 25, 50, 100 and 200 microg ml(-1)) of lectin significantly reduced the percent pupation and percent emergence of B. cucurbitae depicting a negative correlation with the lectin concentration. The LC50 (81 microg ml(-1)) treatment significantly decreased the pupal weight. Moreover, the treatment of larvae had also induced a significant increase in the remaining development duration. The activity of three hydrolase enzymes (esterases, acid and alkaline phosphatases), one oxidoreductase (catalase) and one group transfer enzyme (glutathione S-transferases) was assayed in second instar larvae under the influence of LC50 concentration of lectin for three exposure intervals (24, 48 and 72 hr). It significantly suppressed the activity of all the enzymes after all the three exposure intervals except for esterases which increased significantly.

Effects of plant lectin from cobra lily, Arisaema curvatum Kunth on development of melon fruit fly, Bactrocera cucurbitae (Coq.).

The lectin from tubers of cobra lily, Arisaema curvatum Kunth was purified by affinity chromatography using asialofetuin-linked amino activated porous silica beads. The concentration dependent effect of lectin was studied on second instar larvae (64-72 hr) of Bactrocera cucurbitae (Coq.). The treatment not only resulted in a significant reduction in the percentage pupation and emergence of the adults from treated larvae but it also prolonged the remaining larval development period. A very low LC50 value, 39 mgl(-1) of lectin was obtained on the basis of adult emergence using probit analysis. The activity of three hydrolase enzymes (esterases, acid and alkaline phosphatases), one oxidoreductase (catalase) and one group transfer enzyme (GSTs: Glutathione S-transferases) was assayed in second instar larvae under the influence of the LC50 of lectin at increasing exposure intervals (0, 24, 48 and 72 hr). The Arisaema curvatum lectin significantly decreased the activity of all the enzymes except for esterases, where the activity increased as compared to control at all exposure intervals. The decrease in pupation and emergence as well as significant suppression in the activities of two hydrolases, one oxidoreductase and one GST enzyme in treated larvae of B. cucurbitae indicated that this lectin has anti-metabolic effect on the melon fruit fly larvae.

A tuber lectin from Arisaema jacquemontii Blume with anti-insect and anti-proliferative properties.

A tuber lectin from Arisaema jacquemontii Blume belonging to family Araceae was purified by employing a single step affinity chromatography using column of asialofetuin-linked amino activated silica beads and the bound lectin was eluted with 100 mM glycine-HCl buffer pH 2.5. The purified A. jacquemontii lectin (AJL) showed a single protein band with an apparent molecular mass of 13.4 kDa when submitted to SDS-polyacrylamide gel electrophoresis under reducing as well as non-reducing conditions. The native molecular mass of AJL determined by gel filtration on a Biogel P-200 column was 52 kDa and its carbohydrate content was estimated to be 3.40%. Thus AJL is a tetrameric glycoprotein. The purified lectin agglutinated erythrocytes from rabbit but not from human. Its activity was not inhibited by any of the mono- and disaccharides tested except N-acetyl-D-lactosamine having minimal inhibitory sugar concentration (MIC) 25 mM. Among the glycoproteins tested only asialofetuin was found to be inhibitory (MIC125 microg/mL). A single band was obtained in native PAGE at pH 4.5 while PAGE at pH 8.3 showed two bands. Isoelectric focusing of AJL gave multiple bands in the pI range of 4.6-5.5. When incorporated in artificial diet AJL significantly affected the development of Bactrocera cucurbitae (Coquillett) larvae indicating the possibility of using this lectin in a biotechnological strategy for insect management of cucurbits. Larvae fed on artificial diet containing sublethal dose of AJL showed a significant decrease in acid phosphatase and alkaline phosphatase activity while esterase activity markedly increased as compared to larvae fed on diet without lectin. Out of various human cancer cell lines employed in sulphorhodamine B (SRB) assay, this lectin was found to have appreciable inhibitory effect on the in vitro proliferation of HCT-15, HOP-62, SW-620, HT-29, IMR-32, SKOV-3, Colo-205, PC-3, HEP-2 and A-549 cancer cell lines by 82, 77, 73, 70, 41, 41, 37, 29, 21 and 21% respectively.

A tuber lectin from Arisaema helleborifolium Schott with anti-insect activity against melon fruit fly, Bactrocera cucurbitae (Coquillett) and anti-cancer effect on human cancer cell lines.

An anti-insect and anti-cancer lectin has been isolated from Arisaema helleborifolium Schott by affinity chromatography using asialofetuin-linked amino activated silica beads. The bound A. helleborifolium lectin (AHL) was eluted with 100mM glycine-HCl buffer, pH 2.5. It gave a single band on SDS-PAGE, pH 8.3, and PAGE, pH 4.5. However, multiple bands were obtained in PAGE at pH 8.3 and isoelectric focusing. The lectin was a homotetramer having subunit molecular mass 13.4kDa while its native molecular mass was 52kDa. It was a glycoprotein with 3.40% carbohydrate and was stable up to 60 degrees C for 30min. It showed anti-insect activity towards second instar larvae of Bactrocera cucurbitae (Coquillett) with LC(50) value of 16.4microg/ml. Larvae fed on artificial diet containing sub-lethal dose of AHL showed a significant decrease in acid phosphatase and alkaline phosphatase activity while esterase activity markedly increased as compared to larvae fed on diet without lectin. AHL was also found to inhibit in vitro proliferation of some well established human cancer cell lines viz HOP-62 (95%), HCT-15 (92%), HEP-2 (66%), HT-29 (68%), PC-3 (39.4%), and A-549 (20.7%).