Effect of proline pretreatment on grapevine shoot-tip response to a droplet-vitrification protocol

Equipe DAVEM = Diversité et Adaptation de la Vigne et des Espèces MéditerranéennesProline has been shown to accumulate in plants in response to biotic and abiotic stresses. Exogenous proline has thus been used for improving some plant cryopreservation protocols. Further enhancement of cryopreservation efficiency for in vitro grapevines could be expected if stresses linked to cryopreservation procedures could be reduced. We therefore studied the possible beneficial effect of proline in grapevine cryopreservation. Single-node explants from in vitro grown grapevine plantlets (Vitis vinifera L. cv Portan) were cultured on shooting media (half-strength MS + 1 μM BAP) con- taining no proline (control) or 50, 500, or 2000 μM filter-sterilized L-proline. Shoot tips excised from these micro- shoots were subjected to a PVS2-based droplet-vitrification procedure. Control and rewarmed explants were grown on a recovery medium containing 1 μM BAP. Shoot development on control medium and lower proline concentrations did not notably differ whereas the highest concentration of proline inhibited shoot development. Carry-over effects were observed since lower survival and regrowth were obtained both for non-frozen or LN-treated explants excised from micro-shoots obtained on the 2000 μM proline medium. No significant differences in survival and regrowth were ob- served for non-frozen explants subjected to pretreatment without LN exposure. A slightly enhancing effect (although non-significant) on post-cryopreservation survival was observed for explants derived from shoots developed on 50 or 500 μM proline, but no significant improvement of regrowth percentage was observed for these two conditions. Al- though a slight increase in survival could be observed, no significant beneficial effect of proline pretreatment on post- cryoconservation regrowth could be evidenced in our conditions. However, the 2-week period before explant excision could have allowed at least partial metabolism and catabolism of exogenous proline; the results observed could thus have been the consequence of complex interactions. Shorter proline treatments applied closer to the actual LN exposure step might produce different results and allow for clearer interpretation

Binary self-similar one-dimensional quasilattices: Mutual local-derivability classification and substitution rules

Self-similar binary one-dimensional (1D) quasilattices (QLs) are classified into mutual local-derivability (MLD) classes. It is shown that the MLD classification is closely related to the number-theoretical classification of parameters which specify the self-similar binary 1D QLs. An algorithm to derive an explicit substitution rule, which prescribes the transformation of a QL into another QL in the same MLD class, is presented. An explicit inflation rule, which prescribes the transformation of the self-similar 1D QL into itself, is obtained as a composition of the explicit substitution rules. Symmetric substitution rules and symmetric inflation rules are extensively discussed.Comment: 24 pages, 4 figures, submitted to PR

A Pharmacovigilance Study in Medicine Department of Tertiary Care Hospital in Chhattisgarh (Jagdalpur), India

The aim of the present study was to observe adverse drug reactions (ADRs) with respect to polypharmacy at tertiary care centre at Bastar, Jagdalpur (Government Medical College, Jagdalpur). A prospective, observational evaluation of the ADRs conducted over a period of 6 months in Department of Medicine in Government Medical College, Jagdalpur. During the study period, a total of about 4850 patients visited the OPD and inpatient ward of medicine department, and 154 ADRs events were reported. Out of 154 reports that were identified, a higher percentage of ADRs in females (51.29%) was observed as compared to males (48.7%). Of the 154 ADRs, 76 (49.35%) were found to be mild, 55 moderate (35.71%), and 23 severe (14.93%). A total of 99 (64.28%) ADRs were observed in patients receiving four or more medications concurrently. Conversely 55 (35.71%) ADRs were detected in patients using three or less medicines. The largest number of reports was associated with antimicrobial therapy (28.57%), followed by antihypertensive (24.02%) and antidiabetics (14.28%). Among the affected organ systems, gastrointestinal ADRs constituted a major component (39.61%) followed by skin reactions (28.57%). On causality assessment, nearly 36.36% ADRs were considered as probable, 31.16% possible, and 9.74% could not be categorized and were placed under unassessable. Expected, limited ADR are permissible in normal clinical setting, but the present study focuses on the result showing increased and amplified ADR associated with the polypharmacy practices, which may be curtailed with rational drug prescribing habit

Determinants of potential drug–drug interaction associated dispensing in community pharmacies in the Netherlands

OBJECTIVE: There are many drug–drug interactions (D–DI) of which some may cause severe adverse patient outcomes. Dispensing interacting drug combinations should be avoided when the risks are higher than the benefits. The objective of this study was to identify determinants of dispensing undesirable interacting drug combinations by community pharmacies in the Netherlands. METHODS: A total of 256 Dutch community pharmacies were selected, based on the dispensing of 11 undesirable interacting drug combinations between January 1st, 2001 and October 31st, 2002. These pharmacies were sent a questionnaire by the Inspectorate for Health Care (IHC) concerning their process and structure characteristics. MAIN OUTCOME MEASURE: The number of times the 11 undesirable interacting drug combinations were dispensed. RESULTS: Two hundred and forty-six questionnaires (response rate 96.1%) were completed. Dispensing determinants were only found for the D–DI between macrolide antibiotics and digoxin but not for the other 10 D–DIs. Pharmacies using different medication surveillance systems differed in the dispensing of this interacting drug combination, and pharmacies, which were part of a health care centre dispensed this interacting drug combination more often. CONCLUSION: Medication surveillance in Dutch community pharmacies seems to be effective. Although for most D–DIs no determinants were found, process and structure characteristics may have consequences for the dispensing of undesirable interacting drug combinations

Impact of Small Body Weight on Tenofovir-Associated Renal Dysfunction in HIV-Infected Patients: A Retrospective Cohort Study of Japanese Patients

BACKGROUND: Treatment with tenofovir is sometimes associated with renal dysfunction. Limited information is available on this side effect in patients with small body weight, although the use of tenofovir will spread rapidly in Asia and Africa, where patients are likely to be of smaller body weight. METHODS: In a single-center cohort, Japanese patients with HIV infection who started tenofovir-containing antiretroviral therapy were retrospectively analyzed. The incidence of tenofovir-associated renal dysfunction, defined as more than 25% decrement of estimated glomerular filtration rate (eGFR) from the baseline, was determined. The effects of small body weight and body mass index (BMI) on tenofovir-associated renal dysfunction, respectively, were estimated in univariate and multivariate Cox hazards models as the primary exposure. Other possible risk factors were evaluated by univariate analysis and those found significant were entered into the multivariate analysis. RESULTS: The median weight of 495 patients was 63 kg. Tenofovir-related renal dysfunction occurred in 97 (19.6%) patients (incidence: 10.5 per 100 person-years). Univariate analysis showed that the incidence of tenofovir-related renal dysfunction was significantly associated with smaller body weight and BMI, respectively (per 5 kg decrement, HR = 1.23; 95% CI, 1.10-1.37; p<0.001)(per 1 kg/m(2) decrement, HR = 1.14; 95% CI, 1.05-1.23; p = 0.001). Old age, high baseline eGFR, low serum creatinine, low CD4 count, high HIV viral load, concurrent nephrotoxic drugs, hepatitis C infection, and current smoking were also associated with tenofovir-related renal dysfunction. Multivariate analysis identified small body weight as a significant risk (adjusted HR = 1.13; 95% CI, 1.01-1.27; p = 0.039), while small BMI had marginal significance (adjusted HR = 1.07; 95% CI 1.00-1.16; p = 0.058). CONCLUSION: The incidence of tenofovir-associated renal dysfunction in Japanese patients was high. Small body weight was identified as an independent risk factor for tenofovir-associated renal dysfunction. Close monitoring of renal function is advocated for patients with small body weight treated with tenofovir

Comparison of Bone and Renal Effects In HIV-infected Adults Switching to Abacavir or Tenofovir Based Therapy in a Randomized Trial

Our objective was to compare the bone and renal effects among HIV-infected patients randomized to abacavir or tenofovir-based combination anti-retroviral therapy.In an open-label randomized trial, HIV-infected patients were randomized to switch from zidovudine/lamivudine (AZT/3TC) to abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC). We measured bone mass density (BMD) and bone turnover biomarkers (osteocalcin, osteocalcin, procollagen type 1 N-terminal propeptide (P1NP), alkaline phosphatase, type I collagen cross-linked C-telopeptide (CTx), and osteoprotegerin). We assessed renal function by estimated creatinine clearance, plasma cystatin C, and urinary levels of creatinine, albumin, cystatin C, and neutrophil gelatinase-associated lipocalin (NGAL). The changes from baseline in BMD and renal and bone biomarkers were compared across study arms.Of 40 included patients, 35 completed 48 weeks of randomized therapy and follow up. BMD was measured in 33, 26, and 27 patients at baseline, week 24, and week 48, respectively. In TDF/FTC-treated patients we observed significant reductions from baseline in hip and lumbar spine BMD at week 24 (-1.8% and -2.5%) and week 48 (-2.1% and -2.1%), whereas BMD was stable in patients in the ABC/3TC arm. The changes from baseline in BMD were significantly different between study arms. All bone turnover biomarkers except osteoprotegerin increased in the TDF/FTC arm compared with the ABC/3TC arm, but early changes did not predict subsequent loss of BMD. Renal function parameters were similar between study arms although a small increase in NGAL was detected among TDF-treated patients.Switching to TDF/FTC-based therapy led to decreases in BMD and increases in bone turnover markers compared with ABC/3TC-based treatment. No major difference in renal function was observed.Clinicaltrials.gov NCT00647244