Two-step hard acid deprotection/cleavage procedure for solid phase peptide synthesis

A new two-step deprotection/cleavage procedure for t-butoxycarbonyl (Boc) based solid phase peptide synthesis is reported. First the protective groups are removed from 4-(oxymethyl)-phenylacetamidomethyl (PAM) resin attached peptide with the weak hard acid, trimethylsilyl bromide-thioanisole/trifluoroacetic acid (TFA). In the second step, the peptide is cleaved from the resin with a stronger hard acid such as trimethylsilvl trifluoromethanesulfonate in TFA or with HF. The method is also shown to deformylate Nⁱⁿ-formyltryptophan moiety efficiently. The usefulness of this procedure for practical solid phase peptide synthesis is demonstrated by comparison with other deprotection methods in the synthesis of urotensin II and human endothelin.     

High dose chemotherapy including paclitaxel (T-ICE) combined with peripheral blood stem cell transplantation for male germ cell tumor. Preliminary report

AIM: To evaluate the feasibility and usefulness of high dose chemotherapy including paclitaxel (T-ICE) combined with peripheral blood stem cell transplantation (PBSCT) for male germ cell tumor. METHODS: Five male patients with advanced germ cell tumor underwent 1-6 courses of high dose chemotherapy including paclitaxel (T-ICE; 175 mg/m2 of paclitaxel, 1250 mg/m2 of carboplatin, 1500 mg/m2 of etoposide and 7.5 g/m2 of ifosfamide) with PBSCT after 2-3 courses of induction chemotherapy (PEB or VIP). RESULTS: In all patients, serum marker levels decreased to within the normal range by T-ICE. Two patients underwent resection of residual tumor. In one patient, viable cancer cells were detected in resected lymph node tissue and adjuvant chemotherapy was then performed. Although the follow-up period was short (7-15.5 months), four of the five patients (80%) showed no evidence of recurrent disease. No significant differences in side-effects were noted between T-ICE and conventional high dose ICE, which was previously performed in 39 patients at the Division of Urology, Kobe University Graduate School of Medicine, Japan. CONCLUSIONS: High dose chemotherapy, including T-ICE, combined with PBSCT showed an almost identical degree of side-effects as seen in previous high dose chemotherapy without paclitaxel. Although 80% of the patients showed no evidence of disease so far, the efficacy of T-ICE should be evaluated with more patients and longer follow up.     

Incremental Value of Objective Frailty Assessment to Predict Mortality in Elderly Patients Hospitalized for Heart Failure

Background

The impact of frailty on long-term prognosis in patients with heart failure (HF) remains unclear, and there is no simple and objective assessment for it. This study was performed to examine the association between frailty score and clinical outcome in elderly patients hospitalized for HF.

HISTOCHEMICAL STUDY ON OXIDATIVE ENZYME ACTIVITY IN THE BRAIN, PARTICULARLY OF ASTROCYTES, IN SPONTANEOUSLY HYPERTENSIVE RATS

Hanakita J., Hazama F., Amano S., Yamada E. & Handa H. (1980)
Neuropathology and Applied Neurobiology 6, 471–482
Histochemical study on oxidative enzyme activity in the brain, particularly of astrocytes, in spontaneously hypertensive rats
In order to obtain indirect information concerning brain oedema or increased vascular permeability under hypertensive conditions, the enzyme responses of astrocytes in the brains of spontaneously hypertensive rats were histo-chemically investigated. Reactions for oxidative enzymes, such as NADH₂-, NADPH2-tetrazolium reductases and succinate dehydrogenase were performed on SHR brains of various ages. In the hypertensive rats, proliferation, hypertrophy and increased enzyme activity were observed in astrocytes, particularly in the white matter. This activation of astrocytes appeared at 12 13 weeks-of-age and increased with advancing age. These findings suggest that increased vascular permeability of the materials in the smaller molecules begins in the early stage of the development of hypertension before the breakdown of the blood-brain barrier. Many degenerating astrocytes, showing clasmatodendritic changes, were observed in severely oedematous regions or around cystic foci in the white matter. The changes in astrocytic function seem to be related to the development of the parenchymal changes, particularly of the white matter in the chronic hypertensive state.     

Risk of Long‐Term Dual Antiplatelet Therapy Following Drug‐Eluting Stent Implantation in Octogenarians

Objectives

To evaluate the risk of long‐term dual antiplatelet therapy (DAT) following drug‐eluting stent (DES) implantation in octogenarians.

Background

DES implantation requires DAT; however, DAT‐associated risk in octogenarians remains unclear.

Methods

Two‐hundred and six consecutive octogenarians (130 men, 83.3 ± 3.4 years) underwent stent implantation (104 bare metal stents [BMSs] and 102 DESs) and 38.0 ± 13.2 months of follow‐up.

Results

Significantly more DES patients received DAT. The incidence of bleeding events was similar in the DES and BMS groups for 1 year (total: 10.8% vs 5.8%, P = 0.19; major: 4.9% vs 2.9%, P = 0.70). However, after 2 years, significantly more bleeding events occurred in the DES group than the BMS group (total: 2 years, 21.6% vs 9.6%, P = 0.02; 3 years, 29.4% vs 11.5%, P = 0.001; 4 years, 31.4% vs 15.4%, P = 0.007; major: 2 years, 12.7% vs 3.8%, P = 0.04; 3 years, 18.6% vs 5.8%, P = 0.005; 4 years, 19.6% vs 6.7%, P = 0.006). Overall, significantly more total bleeding events (31.4% vs 15.4%, P = 0.007) and major bleeding events (19.2% vs 6.7%, P = 0.006) were observed in the DES group than in the BMS group. The adjusted hazard ratios and 95% confidence intervals (CI) were as follows: total bleeding events, 2.203 (95% CI: 1.065–4.556; P = 0.033); major bleeding events, 4.324 (1.506–12.414; P = 0.007).

Conclusions

DAT was associated with an increased risk of bleeding events in octogenarians after 2 years. DAT discontinuation should be considered for octogenarians 1‐year post‐DES implantation. (J Interven Cardiol 2013;26:114–122)

     

Type C chronic hepatitis associated with thrombocytopenia in two patients

Abstract Portal hypertension in the presence of chronic hepatitis is generally thought to develop during the progression of the chronic hepatitis to cirrhosis. Before the establishment of assays for diagnosing hepatitis C virus infection, such a case of portal hypertension without liver cirrhosis could be misdiagnosed as idiopathic portal hypertension. It had not fully determined whether portal hypertension might precede the onset of cirrhosis in type C chronic hepatitis. This report presents two cases of women with chronic hepatitis C who developed severe thrombocytopenia; each showed splenomegaly and hypersplenism due to portal hypertension. Angiographic study and histological analysis were conducted to determine the cause of the portal hypertension. Histological evaluation showed an intrahepatic presinusoidal block pattern and fibrotic changes in the periportal area, but no evidence of liver cirrhosis or of other incidental complications such as idiopathic portal hypertension. Both of these patients exhibited normal platelet counts after splenectomy. Thus, type C chronic hepatitis can lead to portal hypertension, as demonstrated in these two patients.     

Long-Term Clinical Follow-up after Sirolimus-Eluting Stent versus Bare Metal Stent Implantation in Patients with Acute Coronary Syndrome

Background and Objective: Drug-eluting stents have been shown to reduce the incidence of restenosis and target vessel revascularization (TVR) compared with bare metal stents (BMSs); however, the long-term efficacy of sirolimus-eluting stent (SES) implantation in patients with acute coronary syndrome (ACS) has not been well established. We have investigated the long-term clinical outcome of SES in patients with ACS.
Methods: Consecutive 245 patients with ACS treated by primary stenting within 24 hours after onset were enrolled. There were 128 patients treated with SES and 117 patients were treated with BMS. We evaluated the incidence of major cardiac events (MACE; total death, nonfatal myocardial infarction, TVR) at 3 years, comparing with 8-month clinical outcome.
Results: Eight-month clinical follow-up shows a significantly lower incidence of TVR in the SES group, 3.1% in the SES group versus 9.4% in the BMS group (P = 0.04). At 3-year clinical follow-up, there was no significant difference in the rate of TVR between the two groups, 8.4% versus 12.4% (P = 0.37). Cumulative incidence of total MACE was 9.2% in the SES group compared with 15.9% in the BMS group (P = 0.18). Only one case of stent thrombosis was observed in the SES (late thrombosis), while two cases of stent thrombosis occurred in the BMS group (late and very late thrombosis; P = 0.55).
Conclusion: SES implantation in patients with ACS is associated with favorable long-term clinical outcome with no excess of late stent thrombosis. Further long-term clinical follow-up will be warranted to confirm the safety and efficacy of SES.