Biomedical subjects

A Luts

Publications and source records attributed to A Luts.

51 records · Page 3Linked to original sources

PubMed1990

Subepithelial hydrostatic pressure may regulate plasma exudation across the mucosa.

This study demonstrated in guinea pig tracheal tubes in vitro that small increases in serosal hydrostatic pressure caused significant mucosal crossing of serosal macromolecules. Reversibility and repeatability of this passage agree with inflammatory stimulus-induced appearance of exuded plasma in airway lumen in vivo. Bradykinin, histamine, and terbutaline, which induce and inhibit, respectively, plasma exudation in vivo, were without effect on the present in vitro permeability. Carbachol, similar to histamine, contracted the trachea, and did not increase, but rather decreased the pressure-induced luminal entry of serosal macromolecules. It is proposed that a plasma-exudation-induced hydrostatic pressure load transiently separates epithelial cells, providing a direction-selective and non-injurious intercellular pathway for passage of bulk plasma exudate into the airway lumen. This mechanism would allow potent plasma protein systems to operate on mucosal surfaces at sites of insults without compromising the mucosa as a barrier to luminal solutes.

Animals↗

PubMed1989

Neuronal galanin is widely distributed in the chicken respiratory tract and coexists with multiple neuropeptides.

The mammalian airways are known to be richly innervated by several types of peptide-containing nerve fibers. Galanin-containing fibers are, however, comparatively few. The results of the present immunocytochemical study indicate that the chicken airways receive a notably dense supply of galanin-storing fibers. Other major neuropeptides were neuropeptide Y, vasoactive intestinal peptide and substance P. Nerve fibers containing these peptides were distributed in the trachea, main bronchi, and the lungs. Minor nerve fiber populations contained calcitonin gene-related peptide, enkephalin and gastrin-releasing peptide. In the trachea and main bronchi the majority of peptide-containing nerve fibers was distributed beneath and sometimes also within the epithelium; fibers were fewer in the lamina propria. In the lungs they occurred both in association with the epithelium of small bronchi and in the septa. Adrenergic nerves (using tyrosine hydroxylase as marker) were predominantly distributed in the lamina propria among bundles of smooth muscle and blood vessels. In the nerve fibers associated with the epithelium and in nerve cell bodies in local ganglia of the tracheal wall, galanin was found to coexist with several other neuropeptides (neuropeptide Y, vasoactive intestinal peptide and substance P) suggesting co-expression of multiple neuropeptide genes in the same population of neurons.

Adrenergic Fibers↗

PubMed1989

Peptide-containing nerve fibers in the respiratory tract of the ferret.

The ferret is widely used in functional and neuromorphological studies on the respiratory tract. We have examined the occurrence and distribution of peptide-containing and adrenergic nerve fibers (using dopamine-beta-hydroxylase as a marker). Adrenergic nerve fibers and fibers storing vasoactive intestinal peptide have a widespread distribution along the entire respiratory tract. Adrenergic nerve fibers were found in the lamina propria, as well as around blood vessels and glands and in smooth muscle. Nerve fibers storing vasoactive intestinal peptide occurred in the epithelium, the lamina propria, around blood vessels and glands, and among muscle bundles. Substance P-, neurokinin A- and calcitonin gene-related peptide-containing nerve fibers predominated beneath and within the epithelium along the entire respiratory tract. Neuropeptide Y-containing nerve fibers were prominent among smooth muscle bundles and around glands. The blood vessels in the wall of the airways were richly supplied with peptide-containing nerve fibers and adrenergic fibers. Ganglia located over the outer or dorsal surface of the tracheal wall harbored vasoactive intestinal peptide-containing nerve cell bodies. Substance P and neurokinin A invariably coexisted in the same nerve fibers. Further, coexistence of substance P/neurokinin A and calcitonin gene-related peptide was observed in the nerve fibers associated with the epithelium. Vasoactive intestinal peptide, neuropeptide Y and occasionally also substance P coexisted in the population of nerve fibers associated with blood vessels and smooth muscle. Many adrenergic nerve fibers contained neuropeptide Y.

Adrenergic Fibers↗

PubMed1989

The lack of long-term recovery and reirradiation tolerance in the mouse kidney.

Mouse kidneys were bilaterally irradiated with X-ray doses of either 6 or 10 Gy (equivalent to approximately 30 and 70 per cent of full tolerance respectively). After an interval of 2 or 26 weeks the mice were retreated with a range of test doses given as single or fractionated irradiation schedules. Functional kidney damage was measured (using clearance of [51Cr]EDTA) before retreatment and at monthly intervals up to 1 year after retreatment. Reirradiation tolerance was assessed from dose-response curves for renal damage in retreated mice compared with that in age matched controls which received only the second treatment. Damage from the initial radiation doses progressed, leading to a decreased reirradiation tolerance with time. There was no evidence for any recovery from functional damage in the interval between 2 and 26 weeks. These studies would strongly suggest that reirradiation of a previously irradiated kidney (even after low initial doses below tolerance) is likely to lead to severe renal damage. Despite the poor reirradiation tolerance at 26 weeks, there was no reduction in the capacity for repair of sublethal injury when fractionated irradiation was given to previously irradiated mice compared with controls.

Animals↗

PubMed1989

Effects of capsaicin pretreatment on neuropeptides and salivary secretion of rat parotid glands.

1. 'Atropine-resistant' secretion of saliva in response to parasympathetic stimulation may reflect antidromic activation of sensory nerve fibres. In this investigation, the effect of pretreatment in the rat with capsaicin (total dose of 125 mg kg-1, s.c.), was determined. 2. In the parotid glands substance P (SP)/calcitonin gene-related peptide (CGRP)-containing nerve fibres around ducts and blood vessels disappeared after capsaicin, while periacinar SP-containing fibres (devoid of CGRP) and CGRP-containing fibres (devoid of SP) remained. Vasoactive intestinal peptide (VIP)-containing nerve fibres seemed to be unaffected. The parotid content of SP and CGRP was reduced by 11 and 36% respectively, while that of VIP remained unchanged. 3. The weights of the parotid glands and their sensitivity to the secretagogues methacholine and SP, injected intravenously, were unchanged as was the response to stimulation of the auriculo-temporal nerve in the presence and absence of atropine. 4. In contrast to capsaicin pretreatment, parasympathetic denervation of the parotid gland reduced the weight of the gland and produced an increase in the response to methacholine and SP. 5. For comparison, the effectiveness of the capsaicin treatment on neuropeptide content was determined in the urinary bladder. The bladder of capsaicin-pretreated rats increased in weight (21%) and in VIP content (31%), while the content of SP and CGRP was reduced by 86 and 94%, respectively. SP- and CGRP-containing nerve fibres were virtually eliminated, while VIP-containing nerve fibres seemed unaffected. 6. In conclusion, antidromic activation of primary afferent (capsaicin-sensitive) C-fibres does not contribute significantly to the 'atropine-resistant' secretory response of the parotid gland to stimulation of the parasympathetic nerve.

Animals↗

PubMed1988

Bladder damage in mice after combined treatment with cyclophosphamide and X-rays. The influence of timing and sequence.

The response of the mouse bladder to single doses of cyclophosphamide (CY), X-rays, or their combination was assessed from the development of functional damage (haematuria and increased frequency of urination). For the combined treatments, a single dose of CY (100 mg.kg-1) was given immediately before or at intervals of up to 9 months before irradiation, or at one week to 9 months after irradiation. Damage after X-rays alone was expressed late, with no functional changes earlier than 5 months. CY alone, by contrast, caused a marked increase in urination frequency and haematuria within one week. There was subsequently partial recovery although some residual damage persisted for at least one year. CY given before or after X-rays caused an early, X-ray dose-related expression of damage. These results suggest that the drug precipitated some of the latent radiation injury. There was also a second wave of damage after the combined treatments and the response at 9-12 months was always more severe than after X-rays alone. This increased late damage could be explained in terms of additive drug and radiation toxicities. Since drug given up to 9 months before or after irradiation caused more severe bladder damage than X-rays alone, CY should be avoided in clinical situations where the bladder has been irradiated.

Animals↗

PubMed1988

Renal damage in mice after treatment with cisplatin and x-rays: comparison of fractionated and single-dose studies.

Functional kidney damage in mice was measured after bilateral irradiation with x-rays alone or in combination with cisplatin (c-DDP). A single drug dose (6 mg/kg) was injected 30 minutes before the first of four or eight x-ray doses, given as four fractions per day with a minimum interval of 5 hours between treatments. A 30-fraction schedule was also investigated, with 15 fractions given in the first week (3 fractions per day), followed by a 2-week rest period and another 15 fractions in the fourth week. The c-DDP (4 mg/kg) was administered 30 minutes before the first fraction of each week, giving a total drug dose of 8 mg/kg. Renal function was assessed monthly from 10 to 37 weeks after the start of treatment by the clearance of 51Cr-labeled EDTA. The combined treatment caused more kidney damage than either agent alone for all fractionation schedules. Enhancement of the radiation damage by c-DDP changed only slightly with fractionation; dose enhancement factors were 1.2 for 1 fraction to 1.3 for 30 fractions. Modeling studies showed that this was consistent with the additive toxic effects of the two agents. There was no change in the alpha/beta for renal damage after x-rays plus c-DDP, compared with x-rays alone (alpha/beta = 1.9 Gy), implying that there was no reduction in repair and no modification of the x-ray response by c-DDP.

Animals↗

PubMed1987

Tolerance of previously irradiated mouse kidneys to cis-diamminedichloroplatinum(II).

In this study the tolerance of previously irradiated kidneys to retreatment with chemotherapy was assessed. cis-Diamminedichloroplatinum(II) (c-DDP) was given to groups of mice at 1, 3, or 6 months after bilateral renal irradiation with single doses of 8-14 Gy. Renal function was measured monthly (by clearance of 51Cr ethylenediaminetetraacetic acid) from 4-35 weeks after c-DDP injection and results were compared with function after X-rays alone or drug alone. At early testing times (during the first 11 weeks after c-DDP injection) the renal function of mice given drug at 1 or 3 months after irradiation was very similar to that seen after drug alone. c-DDP given at 6 months caused slightly more damage than either drug or X-rays alone, but these results could be explained in terms of additive toxicities. At later testing times (11-35 weeks after c-DDP injection), renal function was much worse in all animals which had received previous irradiation, with the greatest damage when c-DDP was given 6 months after X-rays. This may be partly due to additional cell killing by the drug causing the expression of subclinical radiation injury. It is also possible that c-DDP pharmacokinetics was altered in animals with previously irradiated kidneys, leading to higher drug exposures in these mice.

Animals↗

PubMed1987

Repair of sublethal radiation injury after multiple small doses in mouse kidney: an estimate of flexure dose.

Functional kidney damage in mice was measured after a series of fractionated X-irradiations. Doses per fraction of 0.75-12.5 Gy were given as 2, 5, 10, 30, 40, 60, or 80 equal doses in a total treatment time of 4 weeks. Renal function (measured by clearance of 51CrEDTA or hematocrit levels) deteriorated progressively, in a dose related manner, from 20 to 46 weeks after the start of treatment. The changes in renal function versus time were fitted by a polynomial regression through all data and interpolated values for 51CrEDTA clearance were then calculated at 30 and 40 weeks after treatment. Steep dose response curves were obtained and these were used to calculate isoeffective doses for the different fractionation schedules. There was a marked increase in total isoeffective doses from 2-30 fractions and these data were well described by a linear quadratic (L.Q.) expression for damage with an alpha/beta ratio of 2.3 +/- 0.2 Gy. There was only a slight increase in the total isoeffect dose as the size of the dose per fraction was decreased below 2 Gy and the measured isoeffect doses after 40 to 80 fractions were lower than predicted on the basis of an L.Q. model assuming complete repair between successive irradiations. The flexure dose for mouse kidneys irradiated 3 times per day was, effectively, 1 to 2 Gy and hyperfractionation using lower doses per fraction did not lead to significant, additional repair.

Animals↗

PubMed1985

Occurrence and distribution of calcitonin gene-related peptide in the mammalian respiratory tract and middle ear.

Nerve fibres displaying immunoreactivity to calcitonin gene-related peptide (CGRP) are abundantly distributed in the respiratory tract of man, dog, cat, guinea-pig, rat and mouse. Numerous fine, beaded CGRP fibres were seen in the middle ear mucosa, and a moderate supply was found in the ear drum. In the nasal mucosa and in the wall of the Eustachian tube CGRP fibres occurred around blood vessels, arteries in particular. A conspicuously rich supply of CGRP fibres was seen beneath and within the epithelium. In addition, a few fibres were seen in smooth muscle bundles and close to sero-mucous glands. In the tracheo-bronchial wall CGRP fibres were distributed beneath and within the epithelium, in vascular and non-vascular smooth muscle and sometimes close to small glands. A few CGRP-immunoreactive endocrine-like cells were, in addition, distributed in the tracheal epithelium of cat, rat and mouse. The trigeminal, spinal and nodose ganglia, studied in rats and guinea-pigs, harboured numerous CGRP-immunoreactive nerve cell bodies. The cervical sympathetic ganglia were devoid of immunoreactive neuronal perikarya. Surgical and chemical (6-hydroxydopamine treatment) sympathectomy did not affect the number and distribution of CGRP fibres. The distribution of CGRP fibres in the respiratory tract suggests that CGRP may take part in sensory transmission. In addition, CGRP may affect the regulation of local blood flow, smooth muscle tone and glandular secretion.

Animals↗

PubMed1985

Nerve fibres containing peptide histidine isoleucine (PHI) in the respiratory tract.

Recent studies have indicated that vasoactive intestinal peptide (VIP) and peptide histidine isoleucine (PHI) are formed by cleavage of a common precursor protein. In the present study we have examined the distribution of nerve fibres displaying PHI-like immunoreactivity in the upper respiratory tract of several mammalian species including man. PHI fibres were found to have the same general distribution as previously described for VIP fibres. These fibres were distributed mainly in the subepithelial connective tissue around both seromucous glands and blood vessels. In the tracheal wall, PHI fibres were also seen in the non-vascular smooth muscle. Sequential immunostaining for PHI and VIP revealed co-existence of the two peptides in the same nerve fibres.

Animals↗

PubMedDate not supplied

Neuropeptides in guinea pig trachea: distribution and evidence for the release of CGRP into tracheal lumen.

The airways of the guinea pig are richly innervated by peptide-containing nerve fibers. Among the most abundant neuropeptides are calcitonin gene-related peptide (CGRP) and substance P (SP), which are stored in nerve fibers located predominantly within and beneath the epithelium, and vasoactive intestinal peptide (VIP), which is located in fibers running mainly among smooth muscle bundles and seromucous glands. Sensory denervation (capsaicin treatment) of adult guinea pigs caused an almost total disappearance of CGRP- and SP-containing nerve fibers, while the density of VIP-containing nerve fibers located in smooth muscle seemed to increase. In the isolated trachea, perfused luminally, CGRP was found to appear in the intraluminal fluid after exposure to capsaicin but not after electrical vagal stimulation. CGRP concentrations in the tracheal wall did not change significantly. Luminally applied CGRP did not affect smooth muscle tension, measured as intraluminal volume changes.

Animals↗

PubMedDate not supplied

Peptidergic innervation of the major salivary glands of the ferret.

In parotid, sublingual and submandibular glands of the ferret, morphological correlates were looked for, using immunocytochemistry, to previous physiological findings showing parasympathetic "atropine-resistant" salivary secretion and neuropeptide-evoked salivation in this species. Nerve fibers storing VIP were numerous in association with acini, ducts and blood vessels, while the number of fibers storing substance P was moderate and those containing CGRP and galanin few; also the number of NPY-containing fibers was low around acini and ducts but relatively high around vessels. Sympathectomy eliminated all NPY- and almost all dopamine beta-hydroxylase-containing fibers. Parasympathectomy of the parotid gland resulted in a total loss of the VIP-containing fibers, and a profound reduction in the number of substance P- and CGRP-containing fibers.

Animals↗

PubMedDate not supplied

Self-inflicted repetitive optic nerve injury: a case report.

PURPOSE: To describe an obsessive-compulsive patient who developed blindness after self-inflicted repetitive optic nerve injury. METHODS: Case report. RESULTS: A myopic 46-year-old male became blind as a result of intermittent rubbing of his eyes, causing stretching of the optic nerves. Extensive ocular, neurologic and systemic work-ups were negative. Cerebral and orbital MR studies showed severe bilateral optic nerve atrophy. Psychiatric evaluation confirmed obsessive-compulsive personality. CONCLUSIONS: Self-inflicted optic nerve injury should be included in the differential diagnosis of progressive optic neuropathy in a young adult.

Blindness↗

PubMedDate not supplied

Adult liver transplantation at UCL: update 2002.

The authors present the results of a single centre study of 587 liver transplants performed in 522 adults during the period 1984-2002. Results have improved significantly over time due to better pre-, peri- and post-transplant care. One, five, ten and fifteen year actuarial survivals for the whole patient group are 81.2; 69.8; 58.9 and 51.2%. The high incidence of de novo tumors (12.3%), of cardiovascular diseases (7.5%) and of end-stage renal function (3.6%) should be further incentives to tailor the immunosuppression to the individual patient and to direct the attention of the transplant physician to the long-term quality of life of the liver recipient.

Adult↗