The recent refinement and computerization of intravital microscopy have permitted us to monitor microcirculation in vivo with minimal invasion. Here, we report on the first findings made with the use of a pencil-lens intravital microscope as applied to the ischemic rat kidney. Peritubular capillary and glomerular blood flow were monitored under basal conditions, during renal artery occlusion, and immediately after release of the clamp. Erythrocyte velocity was calculated as an angle in consecutive spatiotemporal images. Intravital videomicroscopy during the reperfusion period showed intermittent cessation and partial recovery of blood flow in both peritubular and glomerular capillaries. Blood flow was uniformly orthograde under control conditions; however, the retrograde flow occurred on reperfusion. The patency of peritubular capillaries was partially compromised during the early reperfusion period but rapidly recovered. The recovery of glomerular microcirculation occurred faster than that of peritubular capillaries. We suggest that a functional vasculopathy develops very early in the course of ischemia-reperfusion in superficial cortical microvasculature and is more pronounced in peritubular capillaries, thus accounting for the development of patchy injury of tubular epithelia.
The effects of laryngeal mask airway (LMA) insertion and tracheal intubation on circulatory responses were studied in normotensive (n = 24) and hypertensive (n = 22) Les r$percussions de l'insertion du masque laryngd (ML) et de l~ntubation endotrachdale sur la circulation sont dtudides chez des normotendus (n = 24) et des hypertendus (n = 22). Au hasard et h double aveugle, le ML ou le tube endotrachdal est installd apr~s une induction au thiopentone avec relaxation musculaire ~ la succinylcholine. Comparativement aux niveaux initiaux, aussi bien chez les normo-que chez les hypertendus, la frdquence cardiaque (FC), la pression artirielle rnoyenne (PAM) et le produit frdquence-pression augmentent, clue ce soit aprbs l'intubation ou l~nsertion du ML (P < 0,05). Les changements hdmodynamiques sont plus prononcds apr~s l~ntuba-tion qu'aprbs l~nsertion du ML (P < 0,05). Aprbs l~ntubation de la trachde ou l~nsertion du MI_, chez l'hypertendu, la FC augmente de fafon plus marqude que chez le normotendu (P < 0,05). Les concentrations plasmatiques d'adrdnaline et de noradrdnaline augmentent apr~s l~ntubation ou l'insertion du ML comparativement aux valeurs initiales (P < 0,05) tant chez les normo-que chez les hypertendus. L'augmentation de la concentration de noradrdnaline apr~s l~ntubation est plus importante qu'aprds l~nsertion du ML (P < O,05,t Chez aucun des patients, on n'a ddceld dischdmie myocardique ~ I'ECG. Nous concluons que l~nsertion du ML est associde ?t des rdpercussions circulatoires moindres que l'intubation endotrach$ale aussi bien chez les norrno-que chez les hypertendus.Key words EQUIPMENT: laryngeal mask airway; [NTUBATION, TRACHEAL: complications; COMPLICATIONS' . tachycardia, hypertension. Accepted for publication 8th September, 1994. Laryngoscopy and tracheal intubation after induction of anaesthesia are frequently associated with transient hypertension, tachycardia and arrhythmias. Although these haemodynamic responses are probably of little consequence in healthy individuals, they may be more severe and more hazardous in hypertensive patients. ~ Laryngeal mask airway (LMA) insertion, originally described by Brain,2 has recently become widely used in airway management. 3 Insertion of the LMA after induction of anaesthesia causes less haemodynamic change than tracheal intubation. 4,5 However, the effects of LMA insertion after CAN J ANAESTH 1995 / 42:1 / pp 32-6
Stabilisation of fragile oligonucleotides, typically small interfering RNA (siRNA), is one of the most critical issues for oligonucleotide therapeutics. Many previous studies encapsulated oligonucleotides into ~100-nm nanoparticles. However, such nanoparticles inevitably accumulate in liver and spleen. Further, some intractable cancers, e.g., tumours in pancreas and brain, have inherent barrier characteristics preventing the penetration of such nanoparticles into tumour microenvironments. Herein, we report an alternative approach to cancer-targeted oligonucleotide delivery using a Y-shaped block catiomer (YBC) with precisely regulated chain length. Notably, the number of positive charges in YBC is adjusted to match that of negative charges in each oligonucleotide strand (i.e., 20). The YBC rendezvouses with a single oligonucleotide in the bloodstream to generate a dynamic ion-pair, termed unit polyion complex (uPIC). Owing to both significant longevity in the bloodstream and appreciably small size (~18 nm), the uPIC efficiently delivers oligonucleotides into pancreatic tumour and brain tumour models, exerting significant antitumour activity.
Connexins, the constitutive proteins of gap junctions, are considered to be tumour suppressive agents and are often impaired in the tumourigenic processes. In the present study, the expression of connexin 43 (Cx43), which is involved in the control of spermatogenesis through Sertoli/germ cell coupling, has been investigated in human testicular seminoma cells (tumours and the JKT-1 cell line). Cx43 was immunolocalized in the Golgi apparatus without membrane expression and was detected by immunoblotting in JKT-1 as exclusive 70 kD bands. No mutation could be found by sequencing the transcript obtained by RT-PCR. Transfection with a Cx43-V5 vector reproduced the same gel shift, identifying these 70 kD bands as Cx43. The Cx43-70 kD bands were also expressed in normal testicular tissue, associated with the classical 43 kD isoforms. Stable transfection of JKT-1 with a Cx43-GFP vector allowed restoration of Cx43 membrane expression, functional cell coupling, and inhibition of the cell proliferation rate. Storage of Cx43 in the Golgi apparatus may correspond during spermatogenesis to an intermittent physiological process that becomes permanent in malignant seminoma cells as a result of the tumourigenic process. By preventing Cx43 membrane expression, this disrupted traffic may itself participate in tumour promotion.
This report profiled a seminoma cell line established for both in vitro and in vivo experimental systems. Future studies are planned to investigate germ cells using this seminoma line.
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