Glutathione Protection against Irreversible Binding of Diethyistilbestrol in the Hamster Renal Cortex

Hamster renal cortical slices bioactivated the synthetic estrogen,diethylstilbestrol (DES), to reactive metabolites that boundirreversibly to cellular proteins. Incubation of the slicesfor 30 mm at 37°C with 5 mM diethyl maleate prior to theaddition of 50 nM [³H]DES for 60 min increased the nonextractablebinding of [³H]DES metabolites to cellular protein by 150%,whereas addition of 5 mM glutathione (GSH) decreased the irreversiblebinding of [³H]DES by 17%. The addition of the 5 mM GSH to theincubation medium caused a 24% increase in tissue nonproteinsulfhydryl (NP-SH) content as estimated by reaction with Eliman'sreagent after 30 min at 37°C, while the addition of diethylmaleate for the same time period depleted tissue NP-SH levelsby 54%. Kidneys from hamsters treated with the GSH synthesisinhibitor L-buthionine-(S, R)-sulfoximine at a dosage of 1 mmol/kgbody wt for 2 hr had 45% of the NP-SH content as compared withkidneys of saline-treated controls. The irreversible bindingof [³H]DES metabolites was increased by 60% in renal corticalslices from L-buthionine sulfoximine-treated hamsters. Non-extractablebinding of [³H]DES metabolites to renal DNA was not observed.These results sug gest that GSH, the predominate NP-SH in thecell, protects against the irreversible binding of DES metabolitesto cellular macromolecules.     

Artificial Hair Fiber Restoration in the Treatment of Scalp Scars

BACKGROUND: There is presently no treatment for scalp scars that is fully satisfactory. The modalities of treatment currently in use are surgery, hair transplantation, and micropigmentation. Scalp implantation with artificial hair fibers is used by some physicians as an adjunctive treatment. OBJECTIVE: The objective was to assess the utility of artificial hair fibers to treat scalp scars. METHODS: Data were collected by the principal author from 10 hair restoration practitioners who tested polyamide hair fiber (Biofibre CE 0373/TGA by Medicap Ltd., Carpi (MO), Italy) implantation for scalp scars. RESULTS: Artificial hair fiber implantation occurred between June 1996 and December 2000, and observations continued until December 2004. Data from 54 scars from 44 patients treated showed: (1) no complications in 49 scars (90.7%); (2) mild adverse outcomes in 4 scars (7.4%)-temporary superficial inflammation-infection that subsided following topical cortisone and local/systemic antibiotic treatment; and (3) moderately adverse outcomes in 1 scar (1.9%)-significant inflammation and generalized infection requiring removal of artificial implant to alleviate. Occasional minor skin reactions, sebum plugs, and hyperseborrhea were successfully controlled and well accepted by patients. Fiber fall rate was 20% on average per annum. CONCLUSION: Data show that polyamide hair fiber restoration can be considered an adjunctive treatment for scalp scars in selected cases.     

Oral Loading with Propafenone: A Placebo-Controlled Study in Elderly and Nonelderly Patients with Recent Onset Atrial Fibrillation

The efficacy and safety of propafenone as an oral loading dose (600-mg single oral dose) in converting recent-onset atrial fibrillation (≤ 7 days duration) to sinus rhythm were evaluated in a single-blind, placebo-controlled study according to patients' age. Overall, 240 hospitalized patients, NYHA Class ≤ 2 without signs or symptoms of heart failure were enrolled: among patients aged ≤ 60 years, 55 were allocated to propafenone treatment and 59 to placebo, respectively, and among patients aged > 60 years, 64 were allocated to propafenone treatment and 62 to placebo, respectively. Results: In each age group, the likelihood of conversion to sinus rhythm was significantly greater after propafenone compared with plocebo at 3 and 8 hours. For patients aged ≤ 60 years, corresponding odd ratios were 3.78 (95% CI = 1.80–7.92, P = 0.04) at 3 hours and 4.74 (95% CI = 2.12–10.54, P = 0.02) at 8 hours; for patients aged > 60 years odd ratios were 5.03 (95% CI = 2.08–12.12, P = 0.02) at 3 hours and 6.75 (95% CI = 3.28–73.86, P = 0.01) at 8 hours, respectively. Logistic regression analysis showed that conversion to sinus rhythm within 3 hours was predicted by age ≤ 60 years (P = 0.0064) and by propafenone treatment (P < 0.0001), and conversion to sinus rhythm within 8 hours was predicted by age ≤ 60 years (P = 0.0467) and by propafenone treatment (P < 0.0001). The occurrence of adverse effects was observed in 14%-16% of propafenone treated patients and in 8% of placebo treated patients without significant differences according to age. In conclusion, in patients with recent-onset atrial fibrillation without signs of heart failure, propafenone as a single oral loading dose is effective. It is also effective in selected elderly subjects with a favorable safety profile. Moreover, spontaneous conversion to sinus rhythm appears to occur less frequently in elderly patients.     

Improvement of Cardiac Function in Patients with Severe Congestive Heart Failure and Coronary Artery Disease by Dual Chamber Pacing with Shortened AV Delay

Medical therapy often fails to control symptoms of severe heart failure. The possibility of modifying to some degree the global ventricular performance with the implantation of a physiological dual chamber pacemaker, set with a short atrioventricular delay (100 msec), has been adopted in two patients with severe heart failure due to coronary artery disease. The baseline clinical condition of both patients was characterized by leg edema, ascites, dyspnea at rest, or even orthopnea with a functional New York Heart Association (NYHA) class III-IV. Acute measurements of hemodynamic and echocardiographic parameters during stepwise shortening of AV interval guided the pacemaker implantation and setting of AV delay in the chronic phase. Within a few days after pacemaker implantation, both patients considerably improved their clinical status as well as their functional NYHA class, improving to class U in one patient and to class II-III in the other patient. In addition, modification of systolic and diastoJic parameters paralleled these improvements functional class and clinical condition. Pacemaker therapy in severe heart failure refractory to medical therapy can be of considerable benefit in patients whose quality-of-life is severely compromised when pharmacological therapy is no longer effective. Acute hemodynamic and echocardiographic testing is useful in assessing the most appropriate AV delay and pacing mode.     

Changes in quality of life and sexual health are associated with low‐dose peginterferon therapy and disease progression in patients with chronic hepatitis C

Aliment Pharmacol Ther 31 , 719–734

Summary

Background Primary analysis of the Hepatitis C Antiviral Long‐Term Treatment against Cirrhosis (HALT‐C) Trial showed long‐term peginterferon therapy did not reduce complications in patients with chronic hepatitis C and advanced fibrosis or cirrhosis. Aim To assess the effects of long‐term peginterferon therapy and disease progression on health‐related quality of life (HRQOL), symptoms and sexual health in HALT‐C patients. Methods A total of 517 HALT‐C patients received peginterferon alfa‐2a (90 μg/week); 532 received no additional treatment for 3.5 years. Patients were followed up for outcomes of death, hepatocellular carcinoma and hepatic decompensation. Sexual health, SF‐36 scores and symptoms were serially assessed by repeated‐measures analyses of covariance. Results Patients with cirrhosis (n = 427) reported lower general well‐being and more fatigue (P < 0.001) than patients with fibrosis (n = 622). Physical scores declined significantly over time, independent of treatment, and patients with cirrhosis reported lower scores. Vitality scores were lower in those with cirrhosis, and treated patients experienced a greater decline over time than untreated patients; HRQOL rebounded after treatment ended. Patients with a clinical outcome had significantly greater declines in all SF‐36 and symptom scores. Among men, Sexual Health scores were significantly worse in treated patients and in those with a clinical outcome. Conclusion Clinical progression of chronic hepatitis C and maintenance peginterferon therapy led to worsening of symptoms, HRQOL and, in men, sexual health in a large patient cohort followed up over 4 years (NCT00006164).