In vitro Evaluation of Genotoxicity of Avocado (Persea americana) Fruit and Leaf Extracts in Human Peripheral Lymphocytes

Persea americana is much sought after both for the nutritional value of its fruit and the medicinal values of its various plant parts. A chromosomal aberration assay was undertaken to evaluate the potential genotoxicity of crude extracts from avocado fruits and leaves. Chromosomal aberrations were observed in cultured human peripheral lymphocytes exposed to separately increasing concentrations of 50% methanolic extracts of Persea americana fruit and leaves. The groups exposed to leaf and fruit extracts, respectively, showed a concentration-dependent increase in chromosomal aberrations as compared to that in a control group. The mean percentage total aberrant metaphases at 100 mg/kg, 200 mg/kg, and 300 mg/kg concentrations of leaf extract were found respectively to be 58 ± 7.05, 72 ± 6.41, and 78 ± 5.98, which were significantly higher (p < 0.0001 each) than that in the control group (6 ± 3.39). The mean percentage total aberrant metaphases at 100 mg/kg, 200 mg/kg, and 300 mg/kg concentrations of fruit extract were found to be 18 ± 5.49, 40 ± 10.00, and 52 ± 10.20, respectively, which were significantly higher (p = 0.033, p < 0.0001, and p < 0.0001, respectively) than that for control (6 ± 3.39). Acrocentric associations and premature centromeric separation were the two most common abnormalities observed in both the exposed groups. The group exposed to leaf extracts also showed a significant number of a variety of other structural aberrations, including breaks, fragments, dicentrics, terminal deletion, minutes, and Robertsonian translocations. The group exposed to leaf extract showed higher frequency of all types of aberrations at equal concentrations as compared to the group exposed to fruit extract.     

Disorders of menstruation and their effect on the quality of life in women with congenital factor VII deficiency

AIMS AND OBJECTIVES: To review menstrual problems in women with congenital FVII deficiency and to study their effect on the quality of life during menstruation in women with congenital FVII deficiency. METHOD: 14 women with congenital factor VII deficiency registered with the Haemophilia Centre at the Royal Free Hospital were interviewed and their case notes reviewed. All women completed Pictorial Blood assessment Chart (PBAC) for assessment of menstrual blood loss and a quality of life questionnaire during menstruation. Similar questionnaire and PBAC was completed by an age matched healthy control group of 23 women. RESULTS: Median age of study group was 35 yrs and of control group 34 yrs. Median FVII level of the study group was 31.5 IU/dL Two women had severe FVII deficiency (FVII level < 10 IU/dL) and 12 women had mild-moderate FVII deficiency. 57% women (8/14) from study group had menorrhagia (PBAC score > 100) compared with 17% (4/23) women from the control group. Six women (43%) from the study group were diagnosed with anaemia due to heavy periods, compared to two (9%) in the control group. The quality of life scores during menstruation were significantly worse in the women with FVII deficiency, compared to controls. CONCLUSION: Women with factor VII deficiency exhibit a spectrum of bleeding symptoms, menorrhagia being one of the commonest symptoms. This has adverse effect on their quality of life.     

Factors Influencing the Benefit of Adjunctive Devices during Percutaneous Coronary Intervention in ST-Segment Elevation Myocardial Infarction: Meta-Analysis and Meta-Regression

Background: Routine use of adjunctive devices to percutaneous coronary intervention (PCI) for the treatment of patients of ST-segment elevation myocardial infarction (STEMI) is questionable. Also, the clinical characteristics of STEMI patients that can modulate the treatment benefits of adjunctive devices are not fully understood.
Objective: To synthesize the existing literature to summarize the therapeutic benefit of the adjunctive devices and to identify the patient characteristics which relate to this therapeutic benefit.
Methods: We conducted (i) meta-analyses of the randomized controlled trials (RCT) comparing the performance of the adjunctive devices with PCI for three reperfusion-related outcomes: myocardial blush grade (MBG) < 3, failed ST-segment resolution (STR), and Thrombolysis In Myocardial Infarction (TIMI) flow grade < 3; (ii) stepwise meta-regressions of the effect of trial characteristics on between-trial heterogeneity; and (iii) analyses to examine whether the reperfusion-related end-points explained the between-trial difference in cardiac death and major adverse cardiac events (MACE).
Results: Our meta-analyses represent data from 23 RCT and 5,728 subjects. The overall therapeutic benefit attributable ranged from 32 to 35% for the reperfusion-related outcomes, and thrombectomy devices were more beneficial than the distal protection devices. Meta-regression identified gender, receipt of glycoprotein (GP) IIb/IIIa inhibitor, and baseline TIMI flow grade as significant predictors of improved reperfusion across trials. The available clinical trials were individually underpowered and not designed to detect the influence of adjunctive devices on death or MACE.
Conclusions: Routine use of adjunctive devices cannot be recommended. Thrombus burden, treatment with GP IIb/IIIa inhibitors, and gender may modify the reperfusion benefit of adjunctive devices.     

A comparison of vincristine and doxorubicin infusional chemotherapy with methylprednisolone (VAMP) with the addition of weekly cyclophosphamide (C-VAMP) as induction treatment followed by autografting in previously untreated myeloma

In a sequential nonrandomized study, 204 consecutive unselected patients aged < 70 years received induction chemotherapy with infusional vincristine and adriamycin with oral methyl prednisolone (VAMP; n =75) or with additional cyclophosphamide, C-VAMP ( n =129). 38/129 C-VAMP patients also received verapamil during induction as part of a controlled trial with the aim to overcome drug resistance. A median of five courses (range 1–11) of chemotherapy were required before maximal response was attained and this was similar in both groups. An over-all response rate of 71% was noted at the end of induction. The complete remission (CR) rate with C-VAMP was 24%, which was significantly higher ( P =0.04) than the CR rate with VAMP alone (8%). The addition of verapamil did not alter the response rate of C-VAMP. Compliance to VAMP was overall 83% and not affected by the addition of cyclophosphamide. The proportion of patients going on to receive high-dose chemotherapy and an autograft was the same for VAMP and C-VAMP treated patients (71%). The median overall survival (OS) and progression-free survival (PFS) for the whole group were 4.4 years and 2.0 years and no difference in outcome was observed between the different treatment groups. Therefore the addition of weekly cyclophosphamide to VAMP induction therapy has significantly improved the response rates of previously untreated myeloma patients. C-VAMP was not more toxic and did not compromise the chances of receiving an autograft. Verapamil was without influence on any parameters in this study.     

Bluetongue Virus and Double-Stranded RNA Increase Human Vascular Permeability: Role of p38 MAPK

Endothelial cell (EC) involvement in viral hemorrhagic fevers has been clearly established. However, virally activated mechanisms leading to endothelial activation and dysfunction are not well understood. Several different potential mechanisms such as direct viral infection, alterations in procoagulant/anticoagulant balance, and increased cytokine production have been suggested. We utilized a model of EC barrier dysfunction and vascular endothelial leakage to explore the effect of bluetongue virus (BTV), a hemorrhagic fever virus of ruminants, on human lung endothelial cell barrier properties. Infection of human lung EC with BTV induced a significant and dose-dependent decrease in trans-endothelial electrical resistance (TER). Furthermore, decreases in TER occurred in conjunction with cytoskeletal rearrangement, suggesting a direct mechanism for viral infection-mediated endothelial barrier disruption. Interestingly, double-stranded RNA (dsRNA) mimicked the effects of BTV on endothelial barrier properties. Both BTV- and dsRNA-induced endothelial barrier dysfunction was blocked by treatment with a pharmacological inhibitor of p38 MAPK. The induction of vascular permeability by dsRNA treatment or BTV infection was concomitent with induction of inflammatory cytokines. Taken together, our data suggest that the presence of dsRNA during viral infections and subsequent activation of p38 MAPK is a potential molecular pathway for viral induction of hemorrhagic fevers. Collectively, our data suggest that inhibition of p38 MAPK may be a possible therapeutic approach to alter viral-induced acute hemorrhagic diseases.