Synthesis and stabilization of amino and carboxy terminal constrained collagenous peptides

Short collagenous peptides cross-linked at their amino and carboxy termini with Lys-Lys-dimer template(s) were synthesized, and the effect of the cross-linking on their stabilities was investigated by thermal denaturation experiments. Two chemoselective ligations were used for the construction of the amino and the carboxy cross-linked peptides. The thermal transition temperature (T_m) and the standard free energies (ΔG°) of the cross-linked collagenous peptides increased, and the thermal stabilization effect corresponded to an elongation by two units of the Gly-Pro-Hyp triad. The van't Hoff enthalpy (ΔH°) and the entropy (ΔS°) values of the cross-linked peptides increased with chain elongation, although the increments were smaller than those of the linear peptides. When the same chain lengths were compared, the ΔH° was increased and the ΔS° was nearly the same or increased by the cross-linking. These results suggest that the cross-linking of the collagenous peptides with the Lys-Lys-dimer template(s) for stabilization contributes to the enthalpic effect, rather than the entropic effect.     

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.     

Prediction of the Plasma Concentration Profiles of Orally Administered Drugs in Rats on the Basis of Gastrointestinal Transit Kinetics and Absorbability

A new method based on gastrointestinal transit kinetics has been developed for estimation of the absorption profiles of drugs administered orally as aqueous solutions. The utility of the method was evaluated in rats. The gastrointestinal transit profile for each segment was estimated by in-vivo studies using phenol red, an unabsorbable marker. The gastrointestinal transit profile of phenol red was well explained by a linear gastrointestinal transit kinetic model with eight segments. We also introduced the absorption process into the gastrointestinal transit kinetic model and the plasma profile was predicted by the convolution method. The absorbability of drugs in each segment was assessed by an in-situ absorption study. The validity of the model was evaluated for model drugs with different absorption characteristics. The plasma profiles predicted for ampicillin, theophylline and cephalexin were in good agreement with those observed. The overestimated plasma profile of propranolol suggests that the low bioavailability of propranolol is a result of first-pass metabolism by the intestine wall and the liver, because the calculated absolute absorption is almost perfect. This proposed model is also suitable for estimation of segmental absorption, which is useful for the development of drug delivery systems. We have demonstrated that the plasma profile of orally administered drugs can be predicted by use of gastrointestinal transit and segmental absorbability information and that this method is especially useful for estimating separately the effect of absolute absorption and first-pass metabolism on the bioavailability of drugs.     

Diurnal variation in baseline heart rate of anencephalic fetuses

Abstract The diurnal change in baseline fetal heart rate (FHR) of four anencephalic fetuses at 20, 23, 24 and 30 weeks of gestation were examined. The mean baseline FHR in 00.00–06.00 h, 06.00–12.00 h, 12.00–18.00 h and 18.00–24.00 h were compared by one-factor ANOVA and Scheffe's test in each case. The diurnal variations in baseline FHR were recognized in all subjects ( P < 0.01). In 3/4 subjects, the lowest values were at 00.00–06.00 h. The diurnal variation in baseline FHR might be caused by maternal factors because it was present even in the anencephalic fetuses that had no central nervous system having the oscillators of the circadian rhythm.     

Duration of apnoea in anaesthetized children required for desaturation of haemoglobin to 95%: comparison of three different breathing gases

In this study, we compared three gas compositions to determine if the duration of apnoea for Spo₂ to decrease is proportionate to the oxygen fraction of the gas prior to apnoea. Twenty-five patients ASA physical status 1–2 aged two months to 12 years were included in the study. Anaesthesia was induced via a mask with 5% sevoflurane and 66% N₂O in oxygen. After paralysis with vecuronium (0.12 mg·kg^?1, i.v.) the trachea was intubated and anaesthesia was maintained with sevoflurane and N₂O in oxygen. When cardiovascular stability was obtained, the patient was randomly set to breathe one of three gas compositions: 1. oxygen (Fio₂ 1.0), 2. N₂O/O₂ (Fio₂ 0.4), and 3. air/O₂ (Fio₂ 0.4). All three gas compositions included 2–4% of sevoflurane to maintain anaesthesia. After more than eight min of each gas breathing, apnoea was begun by disconnecting the breathing circuit from the tracheal tube. The time from the start of apnoea (Spo₂ 100%) to Spo₂ of 95% (T₉₅) was measured. T₉₅ measured after breathing N₂O/O₂ and air/O₂ were 34.6 ± 5.7 and 28.8 ± 4.7% of that measured after oxygen breathing (P < 0.001 vs oxygen breathing, P < 0.001 vs oxygen and N₂O/O₂ breathing), respectively. Preoxygenation before intubation was validated to delay the haemoglobin desaturation brought about by apnoea. An induction technique using a low Fio₂ will allow rapid haemoglobin desaturation.     

Transient Manifestation of Antegrade Conduction Over a Kent Bundle After Ventricular Pacing

Postventricular Pacing Preexcitation. Antegrade conduction over a Kent bundle was transiently manifested after the cessation of ventricular overdrive pacing in two patients; otherwise, the heart behaved as if it had a concealed accessory pathway. Conventional electrophysiologic study suggested either a longitudinal dissociation of an accessory pathway or closely located double accessory pathways. The mechanism of the transient manifestation of ventricular preexcitation was discussed. (J Cardiovasc Electrophysiol, Vol. 3, pp. 423–430, October 1992)     

Case Report: Primary splenic non-Hodgkin's B cell lymphoma in a patient with chronic hepatitis C

A case of primary splenic lymphoma in a patient with chronic hepatitis C is reported. A 69-year-old man with chronic hepatitis C was admitted to Fukuoka City Hospital for evaluation of an enlarging splenic tumour. In the spleen, ultrasonographic examination revealed a hypoechoic tumour and computed tomography demonstrated a non-enhancing low density area measuring 7 cm in diameter; coeliac angiography revealed a hypovascular tumour. Gallium scintigraphy showed uptake of the radioisotope in the splenic tumour. A splenectomy was performed and the morphological and immunohistochemical findings of this tumour were compatible with those of non-Hodgin's B cell lymphoma. Recently, cases of malignant B cell lymphoma associated with hepatitis C virus infection have been reported. Lymphotropism of hepatitis C virus may play a pathological role in the development of non-Hodgkin's lymphoma. We emphasize the importance of considering lymphoma in the differential diagnosis of extrahepatic disorders during the course of chronic hepatitis C virus infections.     

Usefulness of the Noncontact Mapping System to Elucidate the Conduction Property for the Treatment of Common Atrial Flutter

Background: The functional role of the cavotricuspid isthmus (CTI) for common atrial flutter (cAFL) remains to be elucidated. In the present study, we examined whether the EnSite system (St. Jude Medical, St. Paul, MN, USA), a noncontact mapping system, is useful to evaluate the conduction properties of CTI to minimize radiofrequency (RF) ablation applications for cAFL. Methods: We enrolled 22 consecutive patients with cAFL (64.1 ± 9.5 years old, M/F 21/1) treated with the EnSite system and examined the conduction properties during cAFL and during atrial pacing. In addition, the effectiveness of the system was evaluated in comparison with the conventional ablation group (67 ± 8.9 years old, n = 15, M/F 13/2). Result: In 11 out of the 22 patients, CTI block line was achieved by fewer RF applications on a presumed single activation pathway which the EnSite system showed (point ablation [PA] group), and the remaining 11 patients needed additional linear ablation (additional ablation [AA] group). The number of RF applications in the PA group was significantly smaller than that in the conventional group. During the lower lateral right atrial pacing at a cycle length of 600 ms, the CV of the CTI in the PA group was smaller compared to that in the AA group (1.36 ± 0.61 vs 2.17 ± 0.66 m/s, P < 0.05), although the CV during cAFL (averaged cycle length 245 ± 34 ms) was not different in both groups. Conclusions: These results indicate that targeting the presumed single line identified by EnSite could be an optional therapy for cAFL RF ablation, and diverse conduction properties in CTI are related to the success rate of this procedure. (PACE 2012;35:1464–1471)