Consensus Statement from India on the Renal Benefits of ARNi, SGLT-2i, and Bisoprolol in Chronic Kidney Disease.

Chronic kidney disease (CKD) is a major contributor to morbidity and mortality in India. CKD often coexists with heart failure (HF), diabetes, and hypertension. All these comorbidities are risk factors for renal impairment. HF and CKD are pathophysiologically intertwined, and the deterioration of one can worsen the prognosis of the other. There is a need for safe renal pharmacological therapies that target both CKD and HF and are also useful in hypertension and diabetes. Neurohormonal activation achieved through the activation of the sympathetic nervous system (SNS), the renin-angiotensin-aldosterone system (RAAS), and the natriuretic peptide system (NPS) is fundamental in the pathogenesis and progression of CKD and HF. Angiotensin receptor neprilysin inhibitor (ARNi), sodium-glucose cotransporter 2 inhibitors (SGLT-2i), and selective ß1-blocker (B1B) bisoprolol suppress this neurohormonal activation. They also have many other cardiorenal benefits across a wide range of CKD patients with or without concomitant HF, diabetes, or hypertension. This consensus statement from India explores the place of ARNi, SGLT-2i, and bisoprolol in the management of CKD patients with or without HF and other comorbidities.

Current Place of SGLT2i in the Management of Heart Failure: An Expert Opinion from India.

Heart failure (HF) is a global health concern that is prevalent in India as well. HF is reported at a younger age in Indian patients with comorbidity of type 2 diabetes (T2DM) in approximately 50% of patients. Sodium-glucose cotransporter-2 inhibitors (SGLT2i), originally approved for T2DM, are new guideline-recommended and approved treatment strategies for HF. Extensive evidence highlights that SGLT2i exhibits profound cardiovascular (CV) benefits beyond glycemic control. SGLT2i, in conjunction with other guideline-directed medical therapies (GMDT), has additive effects in improving heart function and reducing adverse HF outcomes. The benefits of SGLT2i are across a spectrum of patients, with and without diabetes, suggesting their potential place in broader HF populations irrespective of ejection fraction (EF). This consensus builds on the updated evidence of the efficacy and safety of SGLT2i in HF and recommends its place in therapy with a focus on Indian patients with HF.

Role of Bisoprolol in Heart Failure Management: A Consensus Statement from India.

In India, heart failure (HF) is an important health concern affecting younger age groups than the western population. A limited number of Indian patients receive guideline-directed medical therapy (GDMT). Selective ß-1 blockers (BB) are one of the GDMTs in HF and play an important role by decreasing the sympathetic overdrive. The BB reduces heart rate (HR) reverse the adverse cardiac (both ventricular and atrial), vascular, and renovascular remodeling seen in HF. Bisoprolol, a ß-1 blocker, has several advantages and can be used across a wide spectrum of HF presentations and in patients with HF and comorbid conditions such as coronary artery disease (CAD), atrial fibrillation (AF), post-myocardial infarction (MI), uncontrolled diabetes, uncontrolled hypertension, and renal impairment. Despite its advantages, bisoprolol is not optimally utilized for managing HF in India. This consensus builds on updated evidence on the efficacy and safety of bisoprolol in HF and recommends its place in therapy with a focus on Indian patients with HF.

Plantaricin LD1 purified from Lactobacillus plantarum LD1 inhibits biofilm formation of Enterococcus faecalis ATCC 29212 in tooth model.

Plantaricin LD1 was purified to homogeneity using activity-guided chromatography. Enterococcus faecalis ATCC 29212 was found to be sensitive to plantaricin LD1 showing 13 ± 0·21 mm zone of growth inhibition. The minimum inhibitory concentration (MIC) was found to be 50 µg ml-1 against Ent. faecalis ATCC 29212. The in vitro biofilm formation by Ent. faecalis ATCC 29212 was observed, which was completely inhibited in the presence of bacteriocin. Similarly, biofilm formation was also observed on the teeth surface showing purple colour, whereas treated-teeth were clean and indicated no biofilm formation. Further, untreated cells of Ent. faecalis ATCC 29212 were found normal and plantaricin LD1-treated cells were ruptured when seen under light microscope, suggesting killing of target cells. These findings have proven the initial leads for antimicrobial and anti-biofilm activity of plantaricin LD1 against Ent. faecalis and its possible application for the treatment of endodontic diseases.

Cardiological Society of India: Document on acute MI care during COVID-19.

The unprecedented and rapidly spreading Coronavirus Disease-19 (COVID-19) pandemic has challenged public health care systems globally. Based on worldwide experience, India has initiated a nationwide lockdown to prevent the exponential surge of cases. During COVID-19, management of cardiovascular emergencies like acute Myocardial Infarction (MI) may be compromised. Cardiological Society of India (CSI) has ventured in this moment of crisis to evolve a consensus document for care of acute MI. However, this care should be individualized, based on local expertise and governmental advisories.

The effect of an intraorifice barrier and base under coronal restorations on the healing of apical periodontitis: a randomized controlled trial.

AIM: To evaluate the effect of intraorifice barriers and bases on the healing of apical periodontitis following root canal treatment in mandibular molars. METHODOLOGY: A total of 120 permanent mandibular molars with necrotic pulps and periapical radiolucencies (PAI score ≥ 3) were recruited. Root canal treatment was performed in all teeth using a standard protocol, following which they were randomly allocated to one of the three treatment groups: intraorifice barrier group: coronal 3-mm gutta-percha was removed and replaced with glass-ionomer cement (GIC) barrier. The floor of the pulp chamber was then sealed with 2-mm-thick GIC base followed by final composite resin restoration; base group: received 2-mm-thick GIC base before placement of composite resin restoration; and control group: had pulp chamber entirely filled with composite resin only. Follow-up was done at 3, 6, 9 and 12 months. Combination of clinical and radiographic parameters were used to assess treatment outcome. The data were analysed using Kruskal-Wallis, chi-square and Wilcoxon signed-rank tests and logistic regression analysis. RESULTS: At the end of 12 months, the base group had the most favourable healing (97.1%), whilst the control group had the least favourable healing (83.8%). The intraorifice barrier group had healing of 92.1%. However, there was no significant difference in healing between groups at the end of the follow-up period (P > 0.05). Additional subgroup analysis revealed a nonsignificant effect of periodontal status and root filling level on periapical healing. CONCLUSION: The use of an additional barrier under permanent restorations did not significantly improve the outcome of primary root canal treatment in posterior teeth after 12 months. However, its influence in the long term requires further evaluation.

2D and 3D radiographic outcome assessment of the effect of guided tissue regeneration using resorbable collagen membrane in the healing of through-and-through periapical lesions - a randomized controlled trial.

AIM: To evaluate the effect of collagen membrane on the healing of through-and-through periapical lesions using 2-dimensional (2D) and 3-dimensional (3D) imaging techniques. METHODOLOGY: Thirty-two patients with periapical radiolucencies measuring at least 10 mm and with confirmed loss of buccal and lingual cortical plates were randomly divided into GTR and control groups. Periapical surgery was performed in both groups, using a resorbable collagen membrane in the GTR group only. 2D healing was evaluated according to Molven's criteria, while 3D healing was assessed using modified PENN 3D criteria, RAC indices and the B index, 12 months after surgery. Data were analysed using Chi-square, Mann-Whitney and Wilcoxon signed rank tests. RESULTS: Thirty patients were analysed at the 12 months follow-up. Both groups had a significant reduction in the size of lesions [92 ± 12% (control) and 86 ± 14% (GTR) in 2D and 85 ± 19% (Control) and 82 ± 13% (GTR) in 3D], with no significant difference between the groups (P > 0.05). A total of 29(14 control, 15 GTR) teeth and 26(13 control, 13 GTR) teeth were classified as success according to Molven's (2D) and modified PENN 3D criteria, respectively, with no significant difference in success between 2D and 3D assessments. RAC indices of 3D images revealed the greatest percentage of complete healing in R scores (55% for Control, 41% for GTR), whereas cortical plate had the lowest percentage of healing (30% for Control, 27% for GTR) (P > 0.05). Only 2 (13%) patients in each group had complete healing using the B index. CONCLUSION: Periapical surgery with or without GTR was a predictable and viable solution for through-and-through lesions. There was no benefit in using a collagen membrane with regard to the outcome of periapical surgery in through-and-through lesions. Both cone beam computed tomography (CBCT) and periapical radiographs (PA) allowed similar assessment of healing after periapical surgery.

Clinical Effectiveness of a Resin-modified Glass Ionomer Cement and a Mild One-step Self-etch Adhesive Applied Actively and Passively in Noncarious Cervical Lesions: An 18-Month Clinical Trial.

OBJECTIVES:: To evaluate the clinical effectiveness of two methods of application of a mild one-step self-etch adhesive and composite resin as compared with a resin-modified glass ionomer cement (RMGIC) control restoration in noncarious cervical lesions (NCCLs). METHODS:: A total of 294 restorations were placed in 56 patients, 98 in each one of the following groups: 1) G-Bond active application combined with Solare-X composite resin (A-1SEA), 2) G-Bond passive application combined with Solare-X composite resin (P-1SEA), and 3) GC II LC RMGIC. The restorations were evaluated at baseline and after six, 12, and 18 months according to the FDI criteria for fractures/retention, marginal adaptation, marginal staining, postoperative sensitivity, and secondary caries. Cumulative failure rates were calculated for each criterion at each recall period. The effect of adhesive, method of application, and recall period were assessed. The Kruskal-Wallis test for intergroup comparison and Friedman and Wilcoxon signed ranks tests for intragroup comparison were used for each criterion ( α=0.05). RESULTS:: The retention rates at 18 months were 93.26% for the A-1SEA group, 86.21% for the P-1SEA group, and 90.91% for the RMGIC group. The active application improved the retention rates compared with the passive application of mild one-step self-etch adhesive; however, no statistically significant difference was observed between the groups. Marginal staining was observed in 13 restorations (1 in A-1SEA, 4 in P-1SEA, and 8 in RMGIC) with no significant difference between the groups. The RMGIC group showed a significant increase in marginal staining at 12 and 18 months from the baseline. There was no significant difference between the groups for marginal adaptation, secondary caries, or postoperative sensitivity. CONCLUSION:: Within the limitations of the study, we can conclude that mild one-step self-etch adhesive followed by a resin composite restoration can be an alternative to RMGIC with similar retention and improved esthetics in restoration of NCCLs. Agitation could possibly benefit the clinical performance of mild one-step self-etch adhesives, but this study did not confirm that the observed benefit was statistically significant.

Solitary fibrous tumor of the ischioanal fossa-a multidisciplinary approach to management with radiologic-pathologic correlation.

Solitary fibrous tumors are primary mesenchymal tumors, which may occur in any part of the body. Overall, these tumors are considered to have intermediate malignant potential with 5- and 10-year metastasis-free and overall disease-specific survival rates of 74% and 55%, and 89% and 73%, respectively (Demicco et al, 2012). Herein we present an unusual case of solitary fibrous tumors involving the ischioanal fossa in a 19-year-old woman with radiologic-pathologic correlation. This case was complicated by extensive tumor vascularity and was thus managed with preoperative embolization followed by en bloc surgical resection.

Characterization of Gladiolus Germplasm Using Morphological, Physiological, and Molecular Markers.

Estimation of variability and genetic relationships among breeding materials is one of the important strategies in crop improvement programs. Morphological (plant height, spike length, a number of florets/spike), physiological (chlorophyll content, chlorophyll fluorescence, and rapid light curve parameters) and Directed amplification of minisatellite DNA (DAMD) markers were used to investigate the relationships among 50 Gladiolus cultivars. Cluster analysis based on morphological data, physiological characteristics, molecular markers, and cumulative data discriminated all cultivars into seven, five, seven, and six clusters in the unweighted pair-group method using arithmetic mean (UPGMA) dendrogram, respectively. The results of the principal coordinate analysis (PCoA) also supported UPGMA clustering. Variations among the Gladiolus cultivars at phenotypic level could be due to the changes in physiology, environmental conditions, and genetic variability. DAMD analysis using 10 primers produced 120 polymorphic bands with 80% polymorphism showing polymorphic information content (PIC = 0.28), Marker index (MI = 3.37), Nei's gene diversity (h = 0.267), and Shannon's information index (I = 0.407). Plant height showed a positive significant correlation with Spike length and Number of florets/spike (r = 0.729, p < 0.001 and r = 0.448, p = 0.001 respectively). Whereas, Spike length showed positive significant correlation with Number of florets/spike (r = 0.688, p < 0.001) and Chlorophyll content showed positive significant correlation with Electron transport rate (r = 0.863, p < 0.001). Based on significant morphological variations, high physiological performance, high genetic variability, and genetic distances between cultivars, we have been able to identify diverse cultivars of Gladiolus that could be the potential source as breeding material for further genetic improvement in this ornamental crop.

Effect of continuous ultrasonic irrigation on postoperative pain in mandibular molars with nonvital pulps: a randomized clinical trial.

AIM: To evaluate via a randomized clinical trial the effect of continuous ultrasonic irrigation (CUI) on postoperative pain in mandibular molars with nonvital pulps. METHODOLOGY: Seventy mandibular molars with nonvital pulps and apical periodontitis were treated endodontically using two different irrigation techniques. The patients were randomly allocated to one of two groups, CUI (n = 35) and syringe irrigation (SI) (n = 35). The CUI group received irrigant activation using a Proultra Piezoflow ultrasonic needle as the final irrigation protocol, whilst in the SI group, the final irrigation was performed using 27-gauge needle. All the patients were prescribed ibuprofen 400 mg to be taken every 8 h, if required. Postoperative pain using a visual analog scale and analgesic intake were recorded everyday for 7 days. Data were analysed using chi-Square, Mann-Whitney and multiple linear regression tests. RESULTS: Mean postoperative pain was lower in the CUI as compared to SI group, but the difference was significant on the first day only (P = 0.032). The overall 24-h pain prevalence was 41.4%. CUI had a lower incidence of pain (31.4%) as compared to the SI group (51.4%), but the difference was not significant (P > 0.05). No significant difference was observed in analgesic consumption between the groups (P > 0.05). Regression analysis revealed a significant association of mean postoperative pain at 24 h with the irrigant protocol (P = 0.017) and preoperative pain (P = 0.000). CONCLUSION: A significant difference was observed between CUI and syringe irrigation on the first postoperative day following chemo-mechanical preparation. However, the benefit observed was not clinically relevant.

Phytochemicals and Cytotoxicity of Launaea procumbens on Human Cancer Cell Lines.

BACKGROUND: The plant Launaea procumbens belongs to the family Asteraceae and traditionally used in the treatment rheumatism, kidney, liver dysfunctions and eye diseases. In the present study Phytochemical analysis and fractions of methanolic extract of L. procumbens leaves were tested in vitro for their cytotoxicity. OBJECTIVES: Phytochemical analysis and cytotoxic activity of methanolic extract and fractions of Launaea procumbens against four cancer cell lines K562, HeLa, MIA-Pa-Ca-2 and MCF-2 by SRB assay. MATERIALS AND METHODS: Powdered leaves of Launaea procumbens were extracted sequentially with hexane, ethyl acetate, butanol and water by cold extraction. Phytochemical analysis and cytotoxicity assay were carried out for these fractions using SRB assay against four human cancer cell lines, namely leukemia (K562), cervix (HeLa), pancreatic (MIA-Pa-Ca-2) and breast (MCF-7). RESULTS: Ethyl acetate extract exerts potent cytotoxicity against human leukemia (K562), cervix (HeLa) and breast (MCF-7) cell lines IC50 value of 25.30±0.50, 19.80±0.10 and 36.90±4.90 µg/ml respectively. Moderately cytotoxic effect found in hexane extract IC50 value of 41±8 and 48.20±0.50 µg/ml against leukemia (K562), and breast (MCF-7) cancer cell line respectively. The Chemical composition analyzed by GC-MS showed considerable differences in solvent fractions of Launaea procumbens. CONCLUSION: This study revealed the cytotoxic potential of ethyl acetate and hexane fractions of L. procumbens leaves on different cancer cell lines. SUMMARY: Ethyl acetate and Hexane fractions of Launaea procumbens plant exhibit cytotoxicity. Among the different fractions Ethyl acetate showed relatively higher cytotoxicity.Ethyl acetate found more cytotoxic against leukemia (K 562), cervix (HeLa) and breast (MCF-7) cancer cell lines. Moderete cytotoxicity found in hexane fraction against leukemia (K 562) and breast (MCF-7) cancer cell line.GC-MS results showed L. procumbens is a rich source of 1-H- pyrazole, 1-H-imidazole, ß -amyrin, α -amyrin and lupeol. These compounds may be attributed for the cytotoxic activity. Abbreviations used: SRB: Sulforhodamine B assay, MW: Molecular weight.

Effect of maintaining apical patency on endodontic pain in posterior teeth with pulp necrosis and apical periodontitis: a randomized controlled trial.

AIM: To evaluate the association between apical patency and post-operative pain in posterior teeth with pulp necrosis and apical periodontitis. METHODOLOGY: Sixty-eight patients requiring primary root canal treatment in mandibular first molars with necrotic pulps and apical periodontitis were included. The patients were randomly allocated to one of two groups: patency (n = 34) and nonpatency (n = 34). After administering local anaesthesia, root canal preparation was completed using ProTaper rotary instruments. A size 10 K-file was used as a patency file and carried 1 mm beyond the working length (WL) between each instrument change in the patency group, while it was carried up to WL in the nonpatency group. Patients were asked to record their pain experience on a pain chart daily for 7 days. Three patients (two in the patency group, one in the nonpatency group) did not return with completed pain charts on the subsequent visit, resulting in a total of 65 patients for the final analysis (patency, n = 32; nonpatency, n = 33). Data was analysed using Chi Square test, t-test, Mann-Whitney test and Wilcoxon Signed Ranks test. RESULTS: Overall, 43% of the patients experienced post-operative pain. The patency group had less incidence of pain (34%) as compared to the nonpatency group (52%), but the difference was not significant (P = 0.163). CONCLUSION: Maintenance of apical patency during chemomechanical preparation had no significant influence on post-operative pain in posterior teeth with necrotic pulps and apical periodontitis.

Assessment of genetic diversity in indigenous turmeric (Curcuma longa) germplasm from India using molecular markers.

Curcuma longa L., commonly known as turmeric, is one of the economically and medicinally important plant species. It is predominantly cultivated in the tropical and sub tropical countries. India is the largest producer, and exporter of turmeric in the world, followed by China, Indonesia, Bangladesh and Thailand. In the present study, Directed Amplification of Minisatellite DNA (DAMD) and Inter Simple Sequence Repeats (ISSR), methods were used to estimate the genetic variability in indigenous turmeric germplasm. Cumulative data analysis for DAMD (15) and ISSR (13) markers resulted into 478 fragments, out of which 392 fragments were polymorphic, revealing 82 % polymorphism across the turmeric genotypes. Wide range of pairwise genetic distances (0.03-0.59) across the genotypes revealed that these genotypes are genetically quite diverse. The UPGMA dendrogram generated using cumulative data showed significant relationships amongst the genotypes. All 29 genotypes studied grouped into two clusters irrespective of their geographical affiliations with 100 % bootstrap value except few genotypes, suggesting considerable diversity amongst the genotypes. These results suggested that the current collection of turmeric genotypes preserve the vast majority of natural variations. The results further demonstrate the efficiency and reliability of DAMD and ISSR markers in determining the genetic diversity and relationships among the indigenous turmeric germplasm. DAMD and ISSR profiling have identified diverse turmeric genotypes, which could be further utilized in various genetic improvement programmes including conventional as well as marker assisted breeding towards development of new and desirable turmeric genotypes.

Majorana fermions in ferromagnetic chains on the surface of bulk spin-orbit coupled s-wave superconductors.

Majorana fermion (MF) excitations in solid state system have non-Abelian statistics which is essential for topological quantum computation. Previous proposals to realize MF, however, generally requires fine-tuning of parameters. Here we explore a platform which avoids the fine-tuning problem, namely a ferromagnetic chain deposited on the surface of a spin-orbit coupled s-wave superconductor. We show that it generically supports zero-energy topological MF excitations near the two ends of the chain with minimal fine-tuning. Depending on the strength of the ferromagnetic moment in the chain, the number of MFs at each end, n, can be either one or two, and should be revealed by a robust zero-bias peak (ZBP) of height 2 ne(2)/h in scanning tunneling microscopy (STM) measurements which would show strong (weak) signals at the ends (middle) of the chain. The role of an approximate chiral symmetry which gives an integer topological invariant to the system is discussed.

Cation Homeostasis in Red Cells From Patients With Sickle Cell Disease Heterologous for HbS and HbC (HbSC Genotype).

Sickle cell disease (SCD) in patients of HbSC genotype is considered similar, albeit milder, to that in homozygous HbSS individuals--but with little justification. In SCD, elevated red cell cation permeability is critical as increased solute loss causes dehydration and encourages sickling. Recently, we showed that the KCl cotransporter (KCC) activity in red cells from HbSC patients correlated significantly with disease severity, but that in HbSS patients did not. Two transporters involved in red cell dehydration, the conductive channels Psickle and the Gardos channel, behaved similarly in red cells from the two genotypes, but were significantly less active in HbSC patients. By contrast, KCC activity was quantitatively greater in HbSC red cells. Results suggest that KCC is likely to have greater involvement in red cell dehydration in HbSC patients, which could explain its association with disease severity in this genotype. This work supports the hypothesis that SCD in HbSC patients is a distinct disease entity to that in HbSS patients. Results suggest the possibility of designing specific treatments of particular benefit to HbSC patients and a rationale for the development of prognostic markers, to inform early treatment of children likely to develop more severe complications of the disease.

Talc based exopolysaccharides formulation enhancing growth and production of Hellianthus annuus under saline conditions.

Stress tolerating strain of Pseudomonas aeruginosa PF07 possessing plant growth promoting activity was screened for the production of exopolysaccharides (EPS). EPS production was monitored in the cell free culture supernatant (CFCS) and extracted EPS was further purified by thin layer chromatography. EPS producing cells were taken to design talc based formulation and its efficacy was checked on oilseed crop sunflower (Hellianthus annuus), under in vivo saline conditions (soil irrigated with 125 mM of saline water). Application of bioformulation significantly enhanced the yield and growth attributes of the plant in comparison to control (untreated seeds) under stress and non—stress conditions. Germination rate, plant length, dry weight and seed weight increased remarkably. The above findings suggest the application and benefits of utilizing EPS formulation in boosting early seedling emergence, enhancing plant growth parameters, increasing seed weight and mitigating stress in saline affected regions. Such bioformulation may enhance RAS/RT (Root Adhering Soil to Root Tissue ratio), texture of the soil, increase porosity, improve uptake of nutrients, and hence may be considered as commercially important formulation for renovation of stressed sites and enhancing plant growth.

Effects of o-vanillin on K⁺ transport of red blood cells from patients with sickle cell disease.

Aromatic aldehydes like o-vanillin were designed to reduce the complications of sickle cell disease (SCD) by interaction with HbS, to reduce polymerisation and RBC sickling. Present results show that o-vanillin also directly affects RBC membrane permeability. Both the K(+)-Cl(-) cotransporter (KCC) and the Ca(2+)-activated K(+) channel (or Gardos channel) were inhibited with IC50 of about 0.3 and 1 mM, respectively, with activities almost completely abolished by 5 mM. Similar effects were observed in RBCs treated with the thiol reacting reagent N-ethylmaleimide or with the Ca(2+) ionophore A23187, to circumvent any action via HbS polymerisation. The deoxygenation-induced cation conductance (sometimes termed P(sickle)) was partially inhibited, whilst deoxygenation-induced exposure of phosphatidylserine was completely abrogated. Na(+)/K(+) pump activity was also reduced. Notwithstanding, o-vanillin stimulated K(+) efflux through an unidentified pathway and resulted in reduction in cell volume (as measured by wet weight-dry weight). These actions are relevant to understanding how aromatic aldehydes may affect RBC membrane permeability per se as well as HbS polymerisation and thereby inform design of compounds most efficacious in ameliorating the complications of SCD.

Physiological integration plays key role in cranberry (Ericales: Ericaceae) for tolerance of damage by Dasineura oxycoccana (Diptera: Cecidomyiidae).

Understanding the mechanisms by which plants tolerate herbivory is important in the study of insect-plant interactions. In cranberry, current season growth has been identified as the main source of photosynthate for the developing fruits. Feeding injury by larvae of cranberry tipworm, Dasineura oxycoccana Johnson, disrupts the apical growth of cranberry shoots or uprights, but does not impact fruit output. To study the effects of experimentally depleting photosynthate available from sources other than the current season growth on fruit output, we girdled tipworm-injured uprights. This technique enabled us to estimate the contribution of current season growth in supplying photosynthate to developing fruits in tipworm-injured uprights. The mean fruit weight declined by >55% in those tipworm-injured uprights that were limited to photosynthate from only the current season growth (girdled uprights). The result was consistent between two phenologically different cultivars of cranberry, one a native selection from wild cranberry stands ('Howes') and the other a hybrid ('Stevens'). In addition, fruit weight was positively correlated to current season leaf area in the girdled uprights only. These results strongly suggest that physiological integration among the different sources of photosynthate plays a key role in the tolerance of tipworm feeding injury for fruit output in cranberry.

Inhibitors of second messenger pathways and Ca(2+)-induced exposure of phosphatidylserine in red blood cells of patients with sickle cell disease.

The present work investigates the contribution of various second messenger systems to Ca(2+)-induced phosphatidylserine (PS) exposure in red blood cells (RBCs) from sickle cell disease (SCD) patients. The Ca(2+) dependence of PS exposure was confirmed using the Ca(2+) ionophore bromo-A23187 to clamp intracellular Ca(2+) over 4 orders of magnitude in high or low potassium-containing (HK or LK) saline. The percentage of RBCs showing PS exposure was significantly increased in LK over HK saline. This effect was reduced by the Gardos channel inhibitors, clotrimazole and charybdotoxin. Nevertheless, although Ca(2+) loading in the presence of an outwardly directed electrochemical gradient for K(+) stimulated PS exposure, substantial exposure still occurred in HK saline. Under the conditions used inhibitors of other second messenger systems (ABT491, quinacrine, acetylsalicylic acid, 3,4-dichloroisocoumarin, GW4869 and zVAD-fmk) did not inhibit the relationship between [Ca(2+)] and PS exposure. Inhibitors of phospholipase A2, cyclooxygenase, platelet-activating factor, sphingomyelinase and caspases, therefore, were without effect on Ca(2+)-induced PS exposure in RBCs, incubated in either HK or LK saline.