Identification of fibroin-derived peptides enhancing the proliferation of cultured human skin fibroblasts

We previously reported that the fibroin of the silkworm Bombyx mori enhanced the proliferation of cultured human skin fibroblasts. In this work, the fibroin was digested by chymotrypsin, and the resulting peptide fragments were fractionated and assayed for their biological activity. Two peptides that promoted fibroblast growth were isolated and identified to be VITTDSDGNE and NINDFDED. Both sequences are found in the N-terminal region of the fibroin polypeptide and are thought to be the active principle of fibroblast growth-promoting activity.     

MORPHOLOGICAL AND BIOCHEMICAL STUDIES OF A CASE OF MUCOPOLYSACCHARIDOSIS II (HUNTER'S SYNDROME)

An autopsy case of a 19-year-old boy who had shown typical gargoyle features, strictly consistent with mucopolysaccharidosis type II (Hunter's syndrome) was reported. Histologically, cytoplasmic vacuolar change was found In hepatocytes, sinusoidal epithelium of spleen, follicular cells of thyroid, Sertoli cells of testis, chromophobe cell of pituitary and generalized fibroblast-like cells including meninges, cardiac valve and periosteum. The vacuoles consisting of membrane-bound structures with flocculus protein-like material and occasional electron dense bodies on electron microscopy, were considered to be the site of mucopolysaccharide deposition by histochemical analysis. Deposition of lipid material consistent with so-called membranous cytoplasmic body was observed in the neurons of central, peripheral and autonomic nervous system. Hepatosplenomegaly could be explained by cytoplasmic deposition, but the cause of cardiomegaly remained further to be studied. Biochemically hepatic mucopolysaccharide was identified as heparan sulfate, while in the kidney dermatan sulfate and heparan sulfate were detected. The correlation between morphology and biochemistry, and between deposition and degeneration was discussed.     

The distribution of pituitary adenylate cyclase-activating polypeptide-like immunoreactivity is distinct from helodermin- and helospectin-like immunoreactivities in the rat brain

Pituitary adenylate cyclase-activating polypeptide (PACAP) is an amidated 38-residue polypeptide isolated from the ovine hypothalamus. Helodermin, a 35-amino acid peptide, and helospectins, peptides of 38 and 37 amino acid residues, have been isolated from lizard venom. PACAP, helodermin and helospectins share structural features and have a similar profile of pharmacological effects: they stimulate adenylate cyclase. We studied the distribution and characteristics of PACAP-like immunoreactivity in the rat brain with immunochemical and immunohistochemical methods and compared its distribution with that of helodermin- and helospectin-like immunoreactivities. With radioimmunoassay, the highest concentrations of PACAP-like immunoreactivity were found in the hypothalamus and cerebellum. PACAP-immunoreactive cell bodies were located immunohistochemically in the supraoptic nucleus, paraventricular and periventricular hypothalamic nuclei, and in the central grey. PACAP-immunoreactive fibres and terminals were detected in the medial part of the central nucleus of amygdala, in the median eminence and neurohypophysis, and in the central grey. No PACAP-immunoreactive structures were observed in areas such as the cerebral cortex, hippocampus, or cerebellum. The distribution of PACAP-like immunoreactivity differed considerably from the distribution of helodermin- and helospectin-like immunoreactivities. The results of this study suggest that PACAP is a neuropeptide with a role in the regulation of endocrine function in the hypothalamo-hypophyseal axis.     

Mesp1-nonexpressing cells contribute to the ventricular cardiac conduction system.

Previous fate mapping analysis, using Cre recombinase driven by the Mesp1 locus, revealed that Mesp1 is expressed in almost all of the precursors of the cardiovascular system, including the endothelium, endocardium, myocardium, and epicardium. Mesp1-nonexpressing cells were found to be restricted to the outflow tract cushion and along the interventricular septum (IVS), which is a location that is suggestive of specialized cardiac conduction system (CCS). In our current study, we examined the identity of these IVS cells by using the pattern of beta-galactosidase activity in CCS-lacZ mice. In addition, by crossing Mesp1-Cre and floxed GFP reporter mice with CCS-lacZ mice, we have calculated that approximately 20% of the ventricular CCS within the IVS corresponds to Mesp1-nonexpressing cells. These data suggest that the ventricular CCS is of heterocellular origin. Furthermore, we indicate a possibility that a population of the cells that contribute to the ventricular CCS might be distinguished at an early stage of development.     

Antinociceptive effects of ONO-9902, an enkephalinase inhibitor,after visceral stress condition in rats

Purpose

The present study was designed to examine the antinociceptive effects of orally administered ONO-9902, an enkephalinase inhibitor, on both somatic and visceral pain after visceral stress conditions.

Methods

Twenty six male rats were examined. Tail-flick (TF) and colorectal distension (CD) tests were used to determine somatic and visceral antinociceptive effects, respectively. Measurements were performed in rats under immediate post-stress conditions (group ST; n = 14) and in rats nor under stress conditions (group NST; n = 12). In the stressed group, the same device, CD, for visceral antinociceptive effects was used for visceral stress and was applied with an intracolonic pressure of 60 mmHg for 20 min after drug administration. The TF latency and CD threshold were measured before and at 30, 40, 50, 60 and 90 min after administration of ONO-9902 300 mg · kg^?1 or distilled water.

Results

Orally administered ONO-9902 did not produce any changes in the % maximum possible effect (%MPE) in either TF or CD tests in the unstressed group. In the stressed group, %MPE in the CD test increased 18% and 31% at 30 and 40 min, respectively, after oral administration of ONO-9902 compared with the control group (P < 0.05). However, %MPE to TF test did not alter even after the CD-induced stress condition.

Conclusion

These results suggest that ONO-9902 may have analgesic effects on visceral pain but not on somatic pain under immediate post-stress conditions.     

Postischemic spontaneous hyperthermia and its effects in middle cerebral artery occlusion in the rat

This study examined the time course and effects of postischemic spontaneous hyperthermia after transient and permanent focal ischemia. Rats underwent a 90-min, 120-min, or permanent middle cerebral artery occlusion (MCAO). Body temperatures started rising 15-20 min after MCAO and reached 39-40.5 degrees C during the first hour. Sustained hyperthermia was observed during the rest of the first 24 h. In another experiment, rats were subjected to the same interventions, but a normothermic body temperature was maintained. Spontaneous hyperthermia significantly increased the infarct volumes measured 48 h after MCAO in all groups. Reperfusion 2 h after the onset of ischemia was not beneficial in the hyperthermic animals in contrast to the normothermic group. We also examined the effect of spontaneous hyperthermia on the temporal progression of infarcted and penumbral areas 4, 12, or 48 h after MCAO. During spontaneous hyperthermia, penumbral areas became infarcted areas more rapidly, which was most expressed at 4 h. These findings demonstrate that severe spontaneous hyperthermia can occur in rats after MCAO and that it not only increases the infarct volumes in both transient and permanent ischemia, but also accelerates the incorporation of penumbral areas into necrotic areas, which significantly decreases the window of opportunity for therapeutic interventions.     

Smoking Exposure Is Associated with Serum Vitamin D Deficiency in Children: Evidence from the Japan Environment and Children’s Study

Tobacco smoke exposure is known to lower serum 25-hydroxyvitamin D (25(OH)D) concentrations. This study evaluated the association between passive smoking and vitamin D deficiency (VDD) in young children using data from the Japan Environment and Children’s Study (JECS), the largest birth cohort study in Japan. Information on parental smoking status was extracted from a survey of JECS for children aged 1.5 years and data for serum 25(OH)D concentrations were obtained from blood tests in the Sub-Cohort Study of JECS performed at age 2 years. Logistic regression and linear models were fitted to evaluate the association between these variables. Data were analyzed for 4593 children. After adjusting for covariates, smoke exposure was significantly associated with increased incidence of VDD (OR 1.35; 95% CI, 1.14–1.59) according to the logistic model. The linear model indicated that passive smoking negatively predicted de-seasonalized serum 25(OH)D concentrations (β −0.5; 95% CI −0.95 to −0.08) in children aged 2 years. The results suggest that smoke exposure is a risk factor for VDD in children. Given that VD plays a crucial role in bone metabolism and the immune system, our findings are significant for clinical and public health.     

Risk Factors for Complications Associated with Peripherally Inserted Central Catheters During Induction Chemotherapy for Acute Myeloid Leukemia

Objective Peripherally inserted central catheters (PICCs) are widely used in patients with hematologic malignancies. However, the risks of PICC-related complications during chemotherapy for acute myeloid leukemia (AML) are not fully understood. Methods We conducted a retrospective review of 128 adult patients with AML who received induction therapy by way of PICC insertion between 2012 and 2019. Results The median duration of PICC insertion was 30 days. The incidence rate of catheter-related bloodstream infection (CRBSI) was 2.4% at 30 days, and women were more likely to suffer from CRBSI than men. Local reactions at the insertion site were observed in 56 patients; however, these events did not predict CRBSI. The incidence rates of catheter-related thrombosis (CRT) were 1.6% at 30 days. Obesity put patients at an increased risk for CRT. Unexpected PICC removal occurred in 59 patients, and women were at a higher risk of catheter removal than men. Conclusion Low PICC-related complication rates, possibly associated with high rates of catheter removal, were observed during intensive chemotherapy for AML. Women and obese patients require careful monitoring of their PICC. Procedures to achieve appropriate PICC removal without increasing the complication rate need to be considered.