α-tocopherol supplementation prevents lead acetate and hypoxia-induced hepatic dysfunction

Objective:Lead (Pb) is a long-known poison of environment and industrial origin. Its prolonged exposure affects cellular material and alters cellular genetics and produces oxidative damages. In this study, we investigated the exposure of chronic sustained hypoxia or lead acetate alone or in combination with or without supplementation of α-tocopherol on hepatic oxidative and nitrosative stress in rats.Results:Exposure of both lead and hypoxia showed decreased body weight, altered serum lipid profile, oxidant and enzymatic antioxidants status, serum HIF-1α and VEGF concentrations. Simultaneous α-tocopherol supplementation showed beneficial effects to all these alterations. Histopathological observations also showed hepatic degenerative changes after lead or hypoxia exposure either alone or in combination, but remarkable improvement has been noticed after α-tocopherol supplementation.Conclusion:Supplementation of α-tocopherol is beneficial to counter both lead acetate and hypoxia induced hepatic cytotoxicities possibly by reducing oxidative and nitrosative stress.KEY WORDS: α-tocopherol, hypoxia, lead acetate, nitrosative stress, oxidative stress     

Potentiation of epidermal growth factor-induced differentiation of cultured human placental cells by insulin-like growth factor-I.

Insulin-like growth factor-I (IGF-I) potentiates epidermal growth factor (EGF)-stimulated placental lactogen (hPL) secretion by cultured placental cells. In this study we have examined the effects of EGF and IGF-I, alone or in combination, on the differentiation of placental cells in culture and correlated this differentiation with hPL secretion. Addition of EGF (10 ng/mL) or IGF-I (100 ng/mL) alone in serum-free medium was associated with enlargement of the BhCG-positive (differentiated cytotrophoblast marker) mononucleated trophoblast cells. Concomitant addition of IGF-I and EGF resulted in more marked enlargement of the BhCG-positive cells, aggregation of the enlarged cells, and early syncytiotrophoblast formation. Measurement of hPL in the medium revealed that the stimulatory effect (P less than 0.05) of EGF on hPL secretion by total placental cells was proportional to the stimulatory effect of EGF on cell differentiation, as revealed by the obliteration of its stimulatory effect on hPL by BhCG-positive cells. The augmented stimulatory effect of EGF on hPL secretion by all cells in the presence of IGF-I was decreased (P less than 0.05) when expressed per number of human chorionic gonadotropin (BhCG)-positive cells. The dose-response curves of hPL stimulation by IGF-I in the presence of EGF revealed that the decreased effect of IGF-I on hPL secretion by BhCG-positive-staining cells was due to the difference in magnitude (approximately 1.5 times) of stimulation of BhCG staining of and hPL secretion by the cells. These results extend our previous suggestion that IGF-I in placenta, in addition to its effect on hPL secretion, affects cell differentiation; however, the two effects may not be interdependent.     

Annual cost of care for Crohn's disease: a payor perspective

OBJECTIVE: The aim of this study was to estimate the annual cost of care of patients with Crohn's disease according to treatment setting. METHODS: Using a 1994 integrated claims database, patients with a Crohn's-related medical claim (ICD-9 code 555) from 10/01/94 to 09/30/95 were included in this analysis. These patients were stratified into three mutually exclusive disease severity groups: group 1, required hospitalization for Crohn's; group 2, required chronic glucocorticoid or immunosuppressive drug therapy for >6 months; group 3, all remaining patients. Direct charges (based on reimbursement) and utilization of resources were reported for each group. RESULTS: Six-hundred-seven patients were analyzed: 117(19%) in group 1, 31(5%) in group 2, and 459(76%) in group 3. Average age of all patients was 48 years and 43% of these patients were men. Average annual charges for all patients totaled $12,417. Group I patients experienced the highest mean charges ($37,135), whereas patients in groups 2 and 3 incurred $10,033 and $6,277. Approximately 25% of patients accounted for 80% of the total charges. CONCLUSIONS: Crohn's disease is associated with high cost. Although a minority of Crohn's patients required hospitalization, they tended to have higher utilization and were responsible for a majority of total expenditures. New therapies have the potential to reduce overall cost of care, if they prevent Crohn's-related hospitalizations.     

Workflow and Outcomes of Endovascular Thrombectomy for In-Hospital Stroke a Systematic Review and Meta-Analysis

Background and PurposeAcute strokes due to large vessel occlusion in hospitalized patients is not uncommon. We performed a systematic review and meta-analysis to investigate the timing and outcome of endovascular thrombectomy (EVT) for in-hospital stroke.MethodsWe conducted a meta-analysis of clinical studies published in English until September 2020 in the MEDLINE and Cochrane databases. Studies reporting original data on the characteristics and outcomes of in-hospital stroke patients treated with EVT were included. We extracted data on the time-metrics from last known well (LKW) until reperfusion was achieved. We also collected data on procedural and functional outcomes.ResultsOut of 5093 retrieved studies, 8 were included (2,622 patients). The median age was 71.4 years and median NIHSS score on admission was 16. Patients were mostly admitted to the cardiology service (27.3%). The pooled time from LKW to recognition by staff was 72.9 min (95% CI: 40.7 to 105 min). 25.6% received IV tPA. The mean time from stroke recognition to arterial puncture was 134.5 min (95% CI: 94.9 to 174.1). Successful reperfusion occurred in 82.8.% with a pooled mean time from detection to reperfusion of 193.1 min (95% CI: 139.5 to 246.7). The 90-day independent functional outcome was reported in 42% of patients (95% CI 29 to 55%).ConclusionEVT can be performed safely and successfully for in-hospital strokes. Noticeable delays from LKW to detection and then to puncture are noted. This calls for better stroke pathways to identify and treat these patients.BackgroundStroke in hospitalized patients, referred to as in-hospital stroke (IHS), accounts for 2.2–17% of all strokes.¹ The majority of these are ischemic while intracranial hemorrhage represents 2–11% of all IHS.¹ These patients are expected to have a rapid diagnosis and treatment given the ongoing medical supervision, and therefore favorable outcomes.^1–3 However, existing studies report poor outcomes in patients with IHS with a mortality risk that exceeds that of community-onset stroke (COS): 24.7% vs 9.6%.⁴ Surviving IHS patients are also less likely to be discharged home compared to COS (27.7% vs 49.9%) and to be functionally independent at 3 months (31.0% vs 50.4%).^1–4     

Volatile compounds reveal age: a study of volatile organic compounds released by Chrysomya rufifacies immatures

International Journal of Legal Medicine - Age determination of insects collected from vertebrate remains is an essential step in estimating time since colonization as related to the post-mortem...     

Evaluation of Antiviral Activities of Four Local Malaysian Phyllanthus Species against Herpes Simplex Viruses and Possible Antiviral Target

Nucleoside analogues such as acyclovir are effective antiviral drugs against herpes simplex virus infections since its introduction. However, with the emergence of acyclovir-resistant HSV strains particularly in immunocompromised patients, there is a need to develop an alternative antiherpetic drug and plants could be the potential lead. In this study, the antiviral activity of the aqueous extract of four Phyllanthus species were evaluated against herpes simplex virus type-1 (HSV-1) and HSV-2 in Vero cells by quantitative PCR. The protein expressions of untreated and treated infected Vero cells were studied by 2D-gel electrophoresis and Western blot. This is the first study that reported the antiviral activity of P. watsonii. P. urinaria was shown to demonstrate the strongest antiviral activity against HSV-1 and HSV-2, with SI >33.6. Time-of-addition studies suggested that the extract may act against the early infection stage and the replication stage. Protein expression studies indicated that cellular proteins that are involved in maintaining cytoskeletal structure could be potential target for development of antiviral drugs. Preliminary findings indicated that P. urinaria demonstrated potent inhibitory activity against HSV. Hence, further studies such as in vivo evaluation are required for the development of effective antiherpetic drug.     

Somatomedin receptor of human placenta: solubilization, photolabeling, partial purification, and comparison with insulin receptor

Using a recently isolated human basic somatomedin (basic SM) similar to insulin-like growth factor I (IGF-I), we studied both the photoaffinity-labeled and unlabeled basic-SM receptor solubilized from human placental cell membranes. Unlike the result with the insulin receptor, high yields of soluble basic-SM-binding activity are obtained with Triton X-100. The soluble basic-SM receptor retains high-affinity (Kd approximately 0.3 nM) peptide-specific binding of basic SM, similar to the binding present in particulate placenta membranes; the receptor exhibits a comparatively low affinity for insulin (Kd approximately 3 microM). On Sepharose 6B, like the crude soluble insulin receptor, the basic-SM receptor migrates as a species with an apparent Stokes radius of 7.2 nm; unlike the insulin receptor, the basic-SM receptor does not, under similar conditions, yield a smaller binding species (apparent Stokes radius 3.8 nm). Upon photoaffinity labeling with 125I-labeled basic SM, one principal specifically labeled constituent is detected. Upon gel electrophoresis in the presence of 2-mercaptoethanol, the photolabeled constituent, like the insulin receptor, migrates as a species with an apparent molecular weight of about 140,000; in the absence of reducing agent, a molecular weight greater than 240,000 is observed. Lectin-agarose affinity chromatography yields a 30-fold purification both of the basic-SM-binding activity and the photolabeled constituent. Anti-insulin receptor antibody does not appear to precipitate the basic-SM receptor. We conclude that the basic-SM receptor of human placenta is a glycoprotein, remarkably similar to (an isoreceptor) but distinct from the insulin receptor previously characterized in this tissue.     

Supraventricular arrhythmias limit effective cardiac resynchronization therapy: Diagnosis using intracardiac electrograms and device based pacing maneuvers

Cardiac resynchronization therapy is an effective tool for the treatment of drug-refractory heart failure in patients with left ventricular dysfunction and inter/intra ventricular conduction delay. Supraventricular tachycardias may prevent effect delivery of this therapy. We report three cases in which effective therapy was limited by asymptomatic supraventricular tachycardia. Diagnostic pacing maneuvers were performed via the implanted device to determine the underlying arrhythmia mechanism. These cases highlight the importance of (1) treating supraventricular tachycardias before and after implantation of cardiac devices and (2) using device based programmed stimulation to diagnose the mechanism of supraventricular tachycardias. Dr. Gerstenfeld is supported by a Scientist Development Grant from the American Heart Association.