Vascular changes in the rat brain during chronic hypoxia in the presence and absence of hypercapnia.

Changes in brain vascularity in adult rats during adaptation to chronic normobaric hypoxia with or without elevated CO(2) were morphometrically investigated. Immunohistochemistry with anti-rat endothelial cell antigen (RECA-1) antibody was carried out for the vascular analysis. After the rats were subjected to hypoxia for 2 to 8 weeks (wks)(10 percent O(2) in N(2)), the total area of blood vessels was measured in 6 brain regions. After 2 wks of hypoxia, the blood vessel area was found to be significantly increased in the frontal cortex, striatum, hippocampus, thalamus, cerebellum, and medulla oblongata, by 44% , 96% , 65% , 50% , 102% and 97% , respectively. The ratio of large vessels with an area &#62; 500 micro m(2) was also increased in all brain regions. Hypoxic adaptation in brain vascularity did not change during 8 wks of hypoxia, and the hypoxia-induced levels measured in the vasculature returned to control levels 2 wks after the termination of hypoxia in areas of the brain other than the cortex and thalamus. In addition, hypoxia-induced changes in terms of the total vascular area and vessel size distribution were significantly inhibited by the elevation in CO(2), whereas chronic hypercapnia without hypoxia had no effect on brain vascularity. These findings suggested that adaptations in brain vascularity in response to hypoxia are rapidly induced, and there are regional differences in the reversibility of such vascular changes. Carbon dioxide is a potent suppressor of hypoxia-induced vascular changes, and may play an important role in vascular remodeling during the process of adaptation to chronic hypoxia.</p

Plural growth factors in the supernatant of embryos and adult muscles of chickens

An attempt was made to isolate the cell proliferation stimulation factors in the supernatant of embryo carcases and adult muscles of chickens. Evidence was obtained for the presence of at least two or more stimulating factors in both the embryonic and adult muscular supernatants. These factors did not require a supplement of sera or other supporting agents. Furthermore, the use of the salting-out method with ammonium sulfate revealed two or more growth stimulants in the supernatant of chick cells.</p

Effect of bacterium in the malignant wounds of soft tissue sarcoma

Malignant wounds (MWs) are rare skin lesions, which accompany ulceration, necrosis and infection caused by infiltration or damage by malignant tumor. The present study aimed to investigate the bacterial etiology implicated in MW in soft tissue sarcoma (STS), and the effectiveness of culture‑guided perioperative antibacterial administration. A retrospective evaluation was conducted on medical records of patients who presented with MW between 2006 and 2020. A total of seven patients were included in the present study, in whom all tumors were relatively large (>5 cm) and high‑grade. Subsequently, five patients underwent limb‑sparing surgery, and three patients had distant metastases with a 5‑year overall survival of 71%. Preoperative microbiological sampling from the wound identified 11 different bacterial strains in five patients. The infections were polymicrobial with an average of 2.6 strains isolated per patient (1 aerobic, 1.6 anaerobic bacteria). They were predominantly methicillin‑sensitive Staphylococcus aureus. Patients with MWs from STS reported symptoms, including bleeding (71%), exudation (71%) and malodorous wound (43%) at the initial presentation; these completely resolved after surgery. All but one patient reported pain at the MW site with an average numeric rating scale of 4.4 at presentation that decreased to 1.4 (P=0.14) and 0.6 (P=0.04) one and two weeks after surgery, respectively. The patients had elevated C‑reactive protein (71%), anemia (57%), low albumin (86%) and renal/liver dysfunction (14‑29%). One patient was diagnosed with sepsis. Surgical resection afforded symptomatic relief and resolution of abnormal laboratory values. Although selected antibiotics were administered in four patients based on the preoperative antibiotic sensitivity test, surgical site infection (SSI) occurred in three patients. Therefore, the effectiveness of the selected antibiotics based on the results of the preoperative culture in preventing SSI needs to be investigated in the future. In conclusion, physicians should keep in mind that although surgical resection can improve the symptoms and abnormal values in laboratory examination form MW, it is accompanied with a high rate of SSI and poor prognosis

Unilateral ibotenic acid lesions of the prefrontal cortex reduce rotational behavior in 6-hydroxydopamine-lesioned rats

Rats with 6-hydroxydopamine (6-OHDA)-induced lesions of the substantia nigra are used as a model of Parkinson’s disease (PD), and these “lesioned” rats exhibit a rotational behavior when further injected with apomorphine (APO). We examined whether lesions in the prefrontal cortex (PFC) could modify the rotational behavior in PD model rats. Rats initially received unilateral lesions of the substantia nigra by 6-OHDA injection, and then their rotational behavior was measured. Two PFC lesions were achieved by intracerebral infusions of ibotenic acid, followed by measurement of APOinduced rotation. Rotation was reduced by approximately 30&#65397; after PFC injury. The PFC may have functional infl uences on the basal ganglia and may be involved in the pathophysiology of the rotational behavior of PD model rats

Co-existence of inhibitory and stimulatory factors modulating cell proliferation in rat liver cytoplasm.

Factors that inhibit and stimulate cell proliferation were found to coexist in rat liver supernatant. The inhibitory and stimulatory factors were separated by ethanol fractionation. Both factors were sensitive to heat- and trypsin-treatment. The activity of the inhibitor was diminished by partial hepatectomy. The inhibitor from normal livers inhibited DNA and RNA synthesis in the L-cell system, but the same fraction from regenerating livers caused little or no inhibition of nucleic acid synthesis. The stimulatory factor from regenerating livers had a stronger effect on cell proliferation than that of normal livers. Furthermore, the inhibitor from normal livers depressed DNA synthesis in vivo in regenerating livers

Different expression of macrophages and microglia in rat spinal cord contusion injury model at morphological and regional levels.

Macrophages and microglia are implicated in spinal cord injury, but their precise role is not clear. In the present study, activation of these cells was examined in a spinal cord injury model using 2 different antibodies against ED1 clone and ionized calcium binding adaptor molecule 1 (Iba1). Activation was observed at 1, 4, 8, and 12 weeks after contusion injury and was compared with sham operated controls. Our results indicate that activation could be observed in both the dorsal funiculus and the ventral white matter area in the spinal cord at 5 mm rostral to the epicenter of injury. For both cells, there was a gradual increase in activation from 1-4 weeks, followed by down-regulation for up to 12 weeks. As a result, we could stain macrophages by ED1 and microglia by Iba1. We concluded that macrophages may play a role in the phagocytosis of denatured dendrites after spinal cord injury, while microglia may have some cooperative functions, as they were found scattered near the macrophages.</p

Clinicopathological and histological analysis of secondary malignant giant cell tumors of bone without radiotherapy

Giant cell tumor of bone (GCTB) is an intermediate bone tumor that rarely undergoes malignant transformation. Secondary malignant GCTB (SMGCTB) is defined as a lesion in which high‑grade sarcoma occurs at the site of previously treated GCTB. The present study retrospectively reviewed the medical records of patients with GCTB treated at Okayama University Hospital between April 1986 and April 2020. The clinicopathological and histological features of patients with SMGCTB without prior radiotherapy were investigated. A total of three patients (4%) with SMGCTB were detected, and the tumor sites were the distal ulna, distal femur and sacrum. Two of the patients had been treated with curettage and bone graft, and one had been treated with denosumab. In all cases, the lesions were made up of two components, the conventional GCTB component and the malignant component. The Ki67 labeling index was higher in the malignant components of SMGCTB and metastatic lesions compared with that in primary and recurrent conventional GCTB, or the conventional GCTB component of SMGCTB. Moreover, p53 expression was higher in these same components in patients who underwent curettage and bone grafting; however, there was no difference in the patient that received denosumab treatment. In this patient, clinical cancer genomic profiling revealed loss of CDKN2A, CDKN2B and MTAP expression. All three patients developed distant metastasis. The patients with SMGCTB in the ulna and femur died 13 and 54 months after detection of malignant transformation, respectively. The patient with SMGCTB in the sacrum received carbon‑ion radiotherapy to the sacrum and pazopanib; the treatment was effective and the patient was alive at the last follow‑up 3 years later. In conclusion, p53 may be associated with malignant transformation in GCTB. Future studies should investigate the association of between denosumab treatment and malignant transformation, as well as molecular targeted therapy to improve the clinical outcomes of SMGCTB

Exogenous Basic Fibroblast Growth Factor and Nerve Growth Factor Enhance Sprouting of Acetylcholinesterase Positive Fibers in Denervated Rat Hippocampus

Basic fibroblast growth factor (bFGF) and nerve growth factor (NGF) were administered into the rat brain following unilateral fimbria-fornix transection. Both bFGF and NGF stimulated the sprouting of acetylcholinesterase (AChE) positive fibers in the hippocampus on the lesioned side. Furthermore, a small number of AChE-positive fibers were regenerated even when only the vehicle was administered. Rats treated with NGF as well as control group had only thin fibers, whereas those treated with bFGF had not only thin fibers but also thick fibers. These results indicate that intrinsic NGF is released and acts on damaged neurons directly, while bFGF acts them on directly and/or indirectly after brain injury.</p

Partial purification and biological activities and properties of chick growth factors.

Cellular stimulating factors on cell proliferation in the supernatants of chick embryo carcases and adult muscles were studied. There were plural stimulating factors in embryonic and adult muscular supernatants that promoted cell proliferation without any supplement of sera and other materials. Salting-out methods with ammonium sulfate, ethanol fractionation, and isoelectric precipitation were used to isolate the stimulating factors, and these three methods proved the presence of plural stimulants on cell proliferation in the supernatants of chick embryo and adult muscles. The stimulants had altered physico-chemical properties and biological activities due to embryological development. The embryonic stimulants enhanced the synthesis of DNA and protein remarkably, and RNA synthesis in whole cell systems slightly. The muscular stimulants enhanced protein synthesis without any stimulation of DNA and RNA synthesis. Partial purification of the stimulants from the ethanol fractions was performed by DEAE-cellulose chromatography and Sephadex gel chromatography.</p

In Vivo Analysis of Extracellular Proteins in Rat Brains with a Newly Developed Intracerebral Microdialysis Probe

Peptides and proteins in the extracellular space in the central nervous system were investigated in vivo using an intracerebral microdialysis probe. The molecular cut-off of the hollow fiber which was used for the probe was approximately 100 kDa. We examined recovery rates of several compounds in vitro. The recovery rates of proteins and peptides were between 7-28%, with the exceptions of substance P and insulin-like growth factor I. The recovery rates of monoamines and their metabolites were 22-40%. In in vivo studies, two major proteins with apparent molecular weights of 62 kDa and 12 kDa, and several minor proteins (28 kDa, 43 kDa, 52 kDa and 70 kDa) were detected by SDS-polyacrylamide gel electrophoresis in the dialysate from a probe implanted in the striatum of anesthetized rats. These results suggest that the newly developed, intracerebral microdialysis probe might be useful for investigating the dynamic changes of peptides and proteins in the central nervous system.</p