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1.
J Dermatolog Treat ; 33(2): 789-791, 2022 Mar.
Article in English | MEDLINE | ID: mdl-32586156

ABSTRACT

BACKGROUND: At the end of 2019, an innovative coronavirus caused an outbreak of pneumonia cases in Wuhan, a city Hubei Province of China. Despite the direct effect on the routine of all life aspects, there are no clinical guidelines regarding phototherapy treatment during COVID-19 pandemic and as a result, phototherapies units continued to deliver this therapy for patients worldwide. OBJECTIVE: We wish to explore the phototherapy utilization among dermatologic patients. METHODS: We marked all patients that continue to arrive and being treated during COVID-19 pandemic. RESULTS: From March more than 50% of patients stopped arriving to treatments due to the fear of COVID-19 infection. CONCLUSIONS: COVID-19 has a major implication on chronic dermatology treatments such as phototherapy.


Subject(s)
COVID-19 , Dermatology , Disease Outbreaks , Humans , Pandemics , Phototherapy
2.
Acute Med ; 19(2): 102-105, 2020.
Article in English | MEDLINE | ID: mdl-32840261

ABSTRACT

Ferric carboxymaltose (Ferinject®) is an infusion administered for the treatment of iron deficiency anaemia. A number of previous case reports have shown the occurrence of hypophosphataemia after Ferinject® treatment, supposedly managed though high dose phosphate therapy. This case report highlights the risk associated with, and futility of, managing this adverse effect through high dose phosphate infusion. A review of the available literature suggests that if hypophosphataemia develops as a result of Ferinject®, through upregulation of the renal protein Fibroblast Growth Factor-23, it cannot be readily reversed and on average persists for circa 50 days. Acute medical units should be aware of this - likely underreported - adverse effect, and avoid treating these hypophosphataemic patients with high dose phosphate since it can compound symptoms.


Subject(s)
Hypophosphatemia , Maltose , Ferric Compounds/adverse effects , Humans , Hypophosphatemia/chemically induced , Hypophosphatemia/drug therapy , Hypophosphatemia/epidemiology , Incidence , Maltose/adverse effects , Maltose/analogs & derivatives
3.
Commun Biol ; 3(1): 417, 2020 07 31.
Article in English | MEDLINE | ID: mdl-32737395

ABSTRACT

Visualizing ligand binding interactions is important for structure-based drug design and fragment-based screening methods. Rapid and uniform soaking with potentially reduced lattice defects make small macromolecular crystals attractive targets for studying drug binding using microcrystal electron diffraction (MicroED). However, so far no drug binding interactions could unambiguously be resolved by electron diffraction alone. Here, we use MicroED to study the binding of a sulfonamide inhibitor to human carbonic anhydrase isoform II (HCA II). We show that MicroED data can efficiently be collected on a conventional transmission electron microscope from thin hydrated microcrystals soaked with the clinical drug acetazolamide (AZM). The data are of high enough quality to unequivocally fit and resolve the bound inhibitor. We anticipate MicroED can play an important role in facilitating in-house fragment screening for drug discovery, complementing existing methods in structural biology such as X-ray and neutron diffraction.


Subject(s)
Acetazolamide/chemistry , Carbonic Anhydrase II/chemistry , Drug Evaluation, Preclinical , Microscopy, Electron, Transmission , Acetazolamide/therapeutic use , Carbonic Anhydrase II/antagonists & inhibitors , Crystallography, X-Ray , Electrons , Humans , Ligands , Pharmaceutical Preparations/chemistry
4.
Genes Brain Behav ; 9(4): 390-401, 2010 Jun 01.
Article in English | MEDLINE | ID: mdl-20132318

ABSTRACT

Heterozygous mutations of the human FOXP2 gene are implicated in a severe speech and language disorder. Aetiological mutations of murine Foxp2 yield abnormal synaptic plasticity and impaired motor-skill learning in mutant mice, while knockdown of the avian orthologue in songbirds interferes with auditory-guided vocal learning. Here, we investigate influences of two distinct Foxp2 point mutations on vocalizations of 4-day-old mouse pups (Mus musculus). The R552H missense mutation is identical to that causing speech and language deficits in a large well-studied human family, while the S321X nonsense mutation represents a null allele that does not produce Foxp2 protein. We ask whether vocalizations, based solely on innate mechanisms of production, are affected by these alternative Foxp2 mutations. Sound recordings were taken in two different situations: isolation and distress, eliciting a range of call types, including broadband vocalizations of varying noise content, ultrasonic whistles and clicks. Sound production rates and several acoustic parameters showed that, despite absence of functional Foxp2, homozygous mutants could vocalize all types of sounds in a normal temporal pattern, but only at comparably low intensities. We suggest that altered vocal output of these homozygotes may be secondary to developmental delays and somatic weakness. Heterozygous mutants did not differ from wild-types in any of the measures that we studied (R552H ) or in only a few (S321X ), which were in the range of differences routinely observed for different mouse strains. Thus, Foxp2 is not essential for the innate production of emotional vocalizations with largely normal acoustic properties by mouse pups.


Subject(s)
Aging/genetics , Forkhead Transcription Factors/deficiency , Forkhead Transcription Factors/genetics , Repressor Proteins/deficiency , Repressor Proteins/genetics , Vocalization, Animal/physiology , Acoustic Stimulation , Aging/physiology , Animals , Auditory Perceptual Disorders/genetics , Auditory Perceptual Disorders/metabolism , Auditory Perceptual Disorders/pathology , Codon, Nonsense/genetics , Female , Forkhead Transcription Factors/physiology , Gene Expression Regulation, Developmental , Genetic Carrier Screening , Humans , Male , Mice , Mice, Mutant Strains , Mutation, Missense/genetics , Neuronal Plasticity/genetics , Repressor Proteins/physiology
5.
Dent Update ; 30(7): 370-4, 2003 Sep.
Article in English | MEDLINE | ID: mdl-14558202

ABSTRACT

One hundred and forty one, 27-gauge local anaesthetic needles were collected, each following a single injection of local anaesthetic using four commonly performed local anaesthetic injection techniques. The needles were examined for needle tip damage under the scanning electron microscope. Ten unused needles were used as controls. Bone was contacted in 75 (59%) instances and, of these, 73 (97.3%) showed needle tip deformity. Of the four techniques used, bone contact was commonest with the inferior alveolar nerve block, occurring in 88% of instances.


Subject(s)
Anesthesia, Local/instrumentation , Injections/instrumentation , Needles , Equipment Failure , Equipment Reuse , Humans , Microscopy, Electron, Scanning
6.
Surgery ; 128(4): 564-71, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11015089

ABSTRACT

BACKGROUND: Adenocarcinoma of the stomach and gastroesophageal junction results in substantial morbidity, locoregional recurrence, and death. Surgical procedures, even with adjuvant therapy, have not significantly improved survival. This study evaluated the toxicity, response rate, locoregional control, and survival of patients with locally advanced gastric cancer that was treated with neoadjuvant multimodality therapy. METHODS: Patients with stage IIIA or early stage IV gastric adenocarcinoma received neoadjuvant 5-fluorouracil, Leucovorin, Adriamycin, and Cisplatin and underwent gastrectomy or esophagogastrectomy with intraoperative radiotherapy (IORT; 1000 cGY) to the gastric bed and postoperative radiation therapy. RESULTS: Nine of 15 patients (60%) with transmural extension and/or nodal metastases received IORT. There were 2 pathologically complete responses at the primary site. Eleven of 15 patients (73%) had tumor in perigastric lymph nodes; however, 9 of 15 patients (60%) had mucin-filled nodes without tumor cells. Neoadjuvant treatment did not increase operative morbidity rates. Ten of 15 patients (67%) remain free of disease (median, 27 months; range, 6-60 months). Five patients died 13 to 41 months (median, 17 months) after diagnosis. CONCLUSIONS: Neoadjuvant multimodality therapy with neoadjuvant 5-fluorouracil, Leucovorin, Adriamycin, and Cisplatin, radical resection with IORT, and postoperative radiation therapy is safe, can downstage tumors, provides improved locoregional control, and appears to cause significant tumor regression that may result in long-term survival or cure.


Subject(s)
Adenocarcinoma/therapy , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Cisplatin/administration & dosage , Doxorubicin/administration & dosage , Fluorouracil/administration & dosage , Gastrectomy , Leucovorin/administration & dosage , Stomach Neoplasms/therapy , Adenocarcinoma/mortality , Aged , Aged, 80 and over , Combined Modality Therapy , Esophagectomy , Female , Humans , Intraoperative Care , Lymph Node Excision , Male , Middle Aged , Neoplasm Staging , Stomach Neoplasms/mortality , Survival Analysis
8.
Am J Ophthalmol ; 128(2): 165-72, 1999 Aug.
Article in English | MEDLINE | ID: mdl-10458171

ABSTRACT

PURPOSE: To assess the role of hypoxia in inducing the proliferation, hypertrophy, and dysfunction of Muller cells in detached retina and the effectiveness of supplemental oxygen in limiting these reactions. METHODS: Retinal detachments were produced in the right eye of each of 13 cats; the cats survived surgery for 3 days, during which six were kept in normoxia (room air, 21%) and seven in hyperoxia (70% oxygen). Retinas were labeled for proliferation with an antibody (MIB-1) to a cell cycle protein (Ki-67), for evidence of hypertrophy employing antibodies to the intermediate filament protein glial fibrillary acidic protein (GFAP) and to beta-tubulin and for disturbance of glutamate neurochemistry employing antibodies to glutamate to a glutamate receptor (GluR-2) and to glutamine synthetase. RESULTS: Results from the two animals kept in normoxia after retinal detachment confirmed previous reports that detachment caused the proliferation of Muller cells, the hypertrophy of Muller cell processes, and the disruption of glutamate recycling by Muller cells. Oxygen supplementation during detachment reduced Muller cell proliferation and hypertrophy and reduced the abnormalities in the distributions of glutamate, GluR-2, and glutamine synthetase. CONCLUSIONS: Oxygen supplementation reduced the reaction of retinal Muller cells to retinal detachment, limiting their proliferation and helping to maintain their normal structure and function. In the clinical setting, oxygen supplementation between diagnosis and reattachment surgery may reduce the incidence and severity of glial-based complications, such as proliferative vitreoretinopathy.


Subject(s)
Neuroglia/pathology , Oxygen Inhalation Therapy , Retinal Detachment/prevention & control , Animals , Antigens, Nuclear , Biomarkers , Cats , Cell Cycle/immunology , Cell Division/immunology , Disease Models, Animal , Glial Fibrillary Acidic Protein/immunology , Glial Fibrillary Acidic Protein/metabolism , Glutamate-Ammonia Ligase/immunology , Glutamate-Ammonia Ligase/metabolism , Glutamic Acid/immunology , Glutamic Acid/metabolism , Hypertrophy , Hypoxia/etiology , Hypoxia/metabolism , Hypoxia/pathology , Ki-67 Antigen/immunology , Ki-67 Antigen/metabolism , Neuroglia/metabolism , Nuclear Proteins/immunology , Nuclear Proteins/metabolism , Receptors, AMPA/immunology , Receptors, AMPA/metabolism , Retinal Detachment/complications , Retinal Detachment/metabolism , Retinal Detachment/pathology , Treatment Outcome , Tubulin/immunology , Tubulin/metabolism
9.
Genomics ; 58(3): 281-92, 1999 Jun 15.
Article in English | MEDLINE | ID: mdl-10373326

ABSTRACT

The murine homologue of the human chloride channel gene, CLCN5, defects in which are responsible for Dent disease, has been cloned and characterized. We isolated the entire coding region of mouse Clcn5 cDNA and approximately 45 kb of genomic sequence embracing the gene. To study its transcriptional control, the 5' upstream sequences of the mouse Clcn5 gene were cloned into a luciferase reporter vector. Deletion analysis of 1.5 kb of the 5' flanking sequence defined an active promoter region within 128 bp of the putative transcription start site, which is associated with a TATA motif but lacks a CAAT consensus. Within this sequence, there is a motif with homology to a purine-rich sequence responsible for the kidney-specific promoter activity of the rat CLC-K1 gene, another member of the chloride-channel gene family expressed in kidney. An enhancer element that confers a 10- to 20-fold increase in the promoter activity of the mouse Clcn5 gene was found within the first intron. The organization of the human CLCN5 and mouse Clcn5 gene structures is highly conserved, and the sequence of the murine protein is 98% similar to that of human, with its highest expression seen in the kidney. This study thus provides the first identification of the transcriptional control region of, and the basis for an understanding of the regulatory mechanism that controls, this kidney-specific, chloride-channel gene.


Subject(s)
Chloride Channels/genetics , Fanconi Syndrome/genetics , Urinary Calculi/genetics , X Chromosome/genetics , Amino Acid Sequence , Animals , Base Sequence , COS Cells , DNA/genetics , DNA, Complementary/chemistry , DNA, Complementary/genetics , Enhancer Elements, Genetic , Exons , Female , Gene Expression , Genes/genetics , Genetic Linkage , Humans , Introns , Luciferases/genetics , Luciferases/metabolism , Male , Mice , Mice, Inbred Strains , Molecular Sequence Data , Open Reading Frames , Promoter Regions, Genetic , RNA, Messenger/genetics , RNA, Messenger/metabolism , Recombinant Fusion Proteins/genetics , Sequence Alignment , Sequence Analysis, DNA , Sequence Deletion , Sequence Homology, Amino Acid , Tissue Distribution , Transcription, Genetic
10.
J Biol Chem ; 274(24): 17123-31, 1999 Jun 11.
Article in English | MEDLINE | ID: mdl-10358067

ABSTRACT

We have identified and cloned a novel connective tissue growth factor-like (CTGF-L) cDNA from primary human osteoblast cells encoding a 250-amino acid single chain polypeptide. Murine CTGF-L cDNA, encoding a polypeptide of 251 amino acids, was obtained from a murine lung cDNA library. CTGF-L protein bears significant identity ( approximately 60%) to the CCN (CTGF, Cef10/Cyr61, Nov) family of proteins. CTGF-L is composed of three distinct domains, an insulin-like growth factor binding domain, a von Willebrand Factor type C motif, and a thrombospondin type I repeat. However, unlike CTGF, CTGF-L lacks the C-terminal domain implicated in dimerization and heparin binding. CTGF-L mRNA ( approximately 1.3 kilobases) is expressed in primary human osteoblasts, fibroblasts, ovary, testes, and heart, and a approximately 26-kDa protein is secreted from primary human osteoblasts and fibroblasts. In situ hybridization indicates high expression in osteoblasts forming bone, discrete alkaline phosphatase positive bone marrow cells, and chondrocytes. Specific binding of 125I-labeled insulin-like growth factors to CTGF-L was demonstrated by ligand Western blotting and cross-linking experiments. Recombinant human CTGF-L promotes the adhesion of osteoblast cells and inhibits the binding of fibrinogen to integrin receptors. In addition, recombinant human CTGF-L inhibits osteocalcin production in rat osteoblast-like Ros 17/2.8 cells. Taken together, these results suggest that CTGF-L may play an important role in modulating bone turnover.


Subject(s)
Bone and Bones/metabolism , Growth Substances/metabolism , Intercellular Signaling Peptides and Proteins , Neoplasm Proteins , Osteoblasts/metabolism , Transcription Factors , Amino Acid Sequence , Animals , CCN Intercellular Signaling Proteins , Cell Adhesion , Cloning, Molecular , DNA, Complementary/genetics , Fibrinogen/metabolism , Growth Substances/genetics , Humans , Insulin-Like Growth Factor I/metabolism , Insulin-Like Growth Factor II/metabolism , Mice , Molecular Sequence Data , Multigene Family , Osteocalcin/biosynthesis , Platelet Glycoprotein GPIIb-IIIa Complex/metabolism , Protein Binding , Rats , Receptors, Vitronectin/metabolism , Repressor Proteins , Sequence Homology, Amino Acid , Tissue Distribution
11.
J Pediatr Gastroenterol Nutr ; 25(2): 137-41, 1997 Aug.
Article in English | MEDLINE | ID: mdl-9252898

ABSTRACT

BACKGROUND: Poor linear growth frequently complicates chronic inflammatory bowel disease in children. Circulating inflammatory mediators may play a role in this growth delay. We evaluated the effect of experimental colitis on bone growth in a nutritionally controlled rat model. METHODS: Experimental colitis was induced in male Sprague-Dawley rats (125-150 g) by enema with trinitrobenzene sulfonic acid in 50% ethanol on day 1 and 11 of a 14-day protocol. Control animals were pair-fed and all animals received a liquid rat diet (1 kcal/ml). Twenty-four-hour urine, collected on days 2 and 12 and serum samples, collected at death, were analyzed for calcium, zinc, and magnesium. Serum samples from a separate set of animals were studied for serial interleukin-6 levels. Right proximal tibias were processed for growth-plate histomorphometry, in which linear growth is proportional to the heights of the proliferative zone, and terminal hypertrophic chondrocyte, but inversely proportional to the height of the resting zone. RESULTS: Histology confirmed active inflammation in the animals given trinitrobenzene sulfonic acid. Weight gain and both urinary excretion and serum levels of zinc, calcium, and magnesium did not differ between treatment and nontreatment groups. Histologically, there was impaired linear bone growth. The resting zone was greater in the colitis group (94.5 +/- 32.6 microns versus 3.9 +/- 5.4 microns; p < 0.05); the proliferative zone was smaller in the colitis group (123.7 +/- 18.2 microns versus 78.9 +/- 11.2; p < 0.05 micron); the terminal hypertrophic chondrocyte was reduced in the colitis group (19.5 +/- 1.4 microns versus 28.8 +/- 3.6 microns; p < 0.05). At 6 and 24 hours after induction, the level of interleukin-6 was elevated in the colitis group. CONCLUSIONS: Experimental colitis results in a decreased linear bone growth, independent of nutritional intake. Circulating cytokines derived from intestinal inflammation may contribute to the suppression of bone growth.


Subject(s)
Animal Nutritional Physiological Phenomena , Bone Development/physiology , Colitis/physiopathology , Growth Plate/growth & development , Animals , Biological Assay , Calcium/blood , Calcium/urine , Colitis/blood , Colitis/chemically induced , Colitis/urine , Colon/pathology , Disease Models, Animal , Interleukin-6/blood , Interleukin-6/metabolism , Magnesium/blood , Magnesium/urine , Male , Rats , Rats, Sprague-Dawley , Tibia/growth & development , Time Factors , Weight Gain/physiology , Zinc/blood , Zinc/urine
12.
J Cardiovasc Surg (Torino) ; 38(1): 69-75, 1997 Feb.
Article in English | MEDLINE | ID: mdl-9128126

ABSTRACT

OBJECTIVE: The role of complementary medicine techniques has generated increasing interest in today's society. The purpose of our study was to evaluate the effects of one technique, self-hypnosis, and its role in coronary artery bypass surgery. We hypotesize that self-hypnosis relaxation techniques will have a positive effect on the patient's mental and physical condition following coronary artery bypass surgery. EXPERIMENTAL DESIGN: A prospective, randomized trial was conducted. Patients were followed beginning one day prior to surgery until the time of discharge from the hospital. SETTING: The study was conducted at Columbia Presbyterian Medical Center, a large tertiary care teaching institution. PATIENTS: All patients undergoing first-time elective coronary artery bypass surgery were eligible. A total of 32 patients were randomized into two groups. INTERVENTIONS: The study group was taught self-hypnosis relaxation techniques preoperatively, with no therapy in the control group. MEASURES: Outcome variables studied included anesthetic requirements, operative parameters, postoperative pain medication requirements, quality of life, hospital stay, major morbidity and mortality. RESULTS: Patients who were taught self-hypnosis relaxation techniques were significantly more relaxed postoperatively compared to the control group (p=0.032). Pain medication requirements were also significantly less in patients practising the self-hypnosis relaxation techniques that those who were noncompliant (p=0.046). No differences were noted in intraoperative parameters, morbidity or mortality. CONCLUSION: This study demonstrates the beneficial effects self-hypnosis relaxation techniques on patients undergoing coronary artery bypass surgery. It also provides a framework to study complementary techniques and the limitations encountered.


Subject(s)
Anxiety/prevention & control , Autogenic Training , Coronary Artery Bypass/psychology , Relaxation Therapy , Aged , Anxiety/etiology , Female , Humans , Length of Stay , Male , Middle Aged , Pain, Postoperative/drug therapy , Patient Compliance , Postoperative Complications , Prospective Studies , Quality of Life
13.
J Altern Complement Med ; 1(3): 285-90, 1995.
Article in English | MEDLINE | ID: mdl-9395624

ABSTRACT

The effects of complementary techniques and alternative medicine on allopathic therapies is generating much interest and research. To properly evaluate these techniques, well controlled studies are needed to corroborate the findings espoused by individuals practicing complementary medicine therapies. To this end, we evaluated the role of one of these therapies, self-hypnosis relaxation techniques, in a prospective, randomized trial to study its effects on quality of life after coronary artery bypass surgery. Subjects were randomized to a control group or a study group. Study group patients were taught self-hypnosis relaxation techniques the night prior to surgery. The control group received no such treatment. Patients then underwent routine cardiac management and care. The main endpoint of our study was quality of life, assessed by the Profile of Moods Scale. Results demonstrated that patients undergoing self-hypnosis the night prior to coronary artery bypass surgery were significantly more relaxed than the control group (p = 0.0317). Trends toward improvement were also noted in depression, anger, and fatigue. This study demonstrates the beneficial effects of self-hypnosis relaxation techniques on coronary surgery. This study also identifies endpoints and a study design that can be used to assess complementary medicine therapies. Results of this preliminary investigation are encouraging and demonstrate a need for further well-controlled studies.


Subject(s)
Coronary Artery Bypass/psychology , Hypnosis/methods , Patient Education as Topic , Quality of Life , Self Care/methods , Affect , Aged , Coronary Artery Bypass/adverse effects , Emotions , Female , Humans , Male , Middle Aged , Postoperative Care , Preoperative Care , Prospective Studies
14.
J Biol Chem ; 270(39): 22661-4, 1995 Sep 29.
Article in English | MEDLINE | ID: mdl-7559383

ABSTRACT

Neuropeptide Y (NPY) is a 36-amino acid polypeptide that is widely distributed in the central nervous system and periphery. Pharmacological studies have suggested that there are at least three receptor subtypes, Y1, Y2, and Y3. Cloning of the Y1 subtype has been reported previously. Here we report the isolation by expression cloning of a cDNA encoding a human NPY receptor displaying a pharmacology typical of a Y2 receptor. COS-7 cells transfected with the cDNA express high affinity binding sites for NPY, peptide YY, and NPY13-36, whereas [Leu31,Pro34]NPY binds with lower affinity. The receptor is 381 amino acids in length and has seven putative transmembrane regions typical of G-protein-coupled receptors. Comparison of the amino acid sequence of this Y2 receptor to that of the human Y1 receptor indicates that the two receptors are 31% identical at the amino acid level. Northern blot analyses reveal a single 4-kilobase mRNA species and indicate that the messenger RNA is present in many areas of the central nervous system. NPY induced calcium mobilization and inhibited forskolin-stimulated cAMP accumulation in Chinese hamster ovary cells that stably express the Y2 receptor cDNA, indicating that the recombinant Y2 receptor is functionally coupled to second messenger systems.


Subject(s)
Receptors, Neuropeptide Y/biosynthesis , Amino Acid Sequence , Animals , Base Sequence , Binding Sites , Binding, Competitive , Blotting, Northern , CHO Cells , Cell Line , Chlorocebus aethiops , Cloning, Molecular , Colforsin/pharmacology , Cricetinae , Cyclic AMP/metabolism , DNA, Complementary/biosynthesis , Gene Expression , Gene Library , Humans , Kinetics , Molecular Sequence Data , Neuropeptide Y/metabolism , RNA, Messenger/analysis , RNA, Messenger/biosynthesis , Receptors, Neuropeptide Y/genetics , Recombinant Proteins/biosynthesis , Restriction Mapping , Second Messenger Systems/drug effects , Transfection
15.
Adv Wound Care ; 8(4): 30-2, 34, 38-40 passim, 1995.
Article in English | MEDLINE | ID: mdl-7627418

ABSTRACT

This blinded study describes the effect of ibuprofen (IBU) on experimental pressure ulcers (PU) induced in the fuzzy rat model. Ibuprofen's fibrinolytic activity has been found effective in preserving dermal vasculature in rats following burn injury. Experimental pressure ulcers were generated on the hips of fuzzy rats with the aid of computer control, using five daily, 6-hour pressure sessions. In the first study, 17 rats received intraperitoneal (I.P.) injection of IBU or saline control after each pressure session. In the second study, 44 rats received IBU or control, before, during, and after application of pressure by I.P. or intramuscular (I.M.) injections. Quantitation of histology is based on five prominent lesions, including: ulceration, infarction, panniculus carnosus necrosis, fat atrophy, and deep muscle necrosis. The following hypothesis was tested: Reperfusion injury and vascular occlusion in pressure ulcers may be similar to that which occurs in burns and, therefore, is responsive to IBU intervention. The results indicate that IBU does not have significant effects on the development of pressure ulcers. The mechanisms of IBU action in other organ and tissue systems are discussed in relation to the effect of IBU on the pressure ulcer model.


Subject(s)
Ibuprofen/therapeutic use , Pressure Ulcer/drug therapy , Animals , Disease Models, Animal , Drug Evaluation, Preclinical , Female , Humans , Male , Pressure Ulcer/prevention & control , Rats , Single-Blind Method
16.
J Am Coll Nutr ; 14(3): 258-63, 1995 Jun.
Article in English | MEDLINE | ID: mdl-8586775

ABSTRACT

RATIONALE AND OBJECTIVE: Fish oil, rich in n-3 polyunsaturated fatty acids, can alter leukotriene production and hence neutrophil function, factors which may be important in the inflammation of Crohn's disease (CD). Therefore we studied the effect of dietary PUFA on neutrophil mediated ileal inflammation and neutrophil function in the rat. METHODS: Animals were ad libitum-fed pellet diets containing 9.5% fish oil (menhaden oil, rich in n-3 PUFA) with 0.5% safflower oil, 10% safflower oil (rich in n-6 PUFA) or standard chow (6% fat) for 50 days prior to the study. Weight and circulating leukocyte and total neutrophil counts were identical in all three groups. Neutrophil mediated ileal inflammation induced by formyl-methionyl-leucyl-phenylalanine (fMLP) perfusion was evaluated by measuring macromolecular uptake of radiolabelled dextran (MW 70,000) and changes in mucosal neutrophil infiltration. RESULTS: The fish oil diet group showed no difference in fMLP-induced permeability changes relative to the Chow Control group. However, the Safflower Oil supplemented diet group had a reduced permeability response (p < 0.01). Mirroring the permeability changes, there was diminished mucosal neutrophil infiltration in the Safflower Oil group following ileal perfusion with fMLP (< .005). Chemotaxis and chemiluminescence, two important neutrophil functions, were also significantly suppressed in the Safflower Oil animals (p < 0.05). CONCLUSIONS: The failure of a n-3 PUFA enriched diet to diminish the ileal inflammatory response to a bacterial peptide and suppress neutrophil function in the rat suggests such therapy would not be expected to be highly successful in CD. However, it requires confirmation in man, especially under the more complicated inflammatory conditions found in CD. On the other hand, the decreased neutrophil mediated responses with a high linoleic acid (n-6 PUFA) diet warrant further investigation.


Subject(s)
Fatty Acids, Omega-3/pharmacology , Ileum/metabolism , Neutrophils/physiology , Animals , Chemotaxis, Leukocyte , Crohn Disease/metabolism , Crohn Disease/pathology , Crohn Disease/physiopathology , Dextrans/pharmacokinetics , Disease Models, Animal , Fatty Acids, Omega-3/administration & dosage , Food, Fortified , Ileum/cytology , Ileum/physiology , Leukotrienes/metabolism , Linoleic Acid , Linoleic Acids/pharmacology , Luminescent Measurements , Male , N-Formylmethionine Leucyl-Phenylalanine/pharmacology , Neutrophils/drug effects , Permeability , Rats , Rats, Sprague-Dawley
17.
Nature ; 372(6508): 739-46, 1994.
Article in English | MEDLINE | ID: mdl-7997261

ABSTRACT

Production of interleukin-1 and tumour necrosis factor from stimulated human monocytes is inhibited by a new series of pyridinyl-imidazole compounds. Using radiolabelled and radio-photoaffinity-labelled chemical probes, the target of these compounds was identified as a pair of closely related mitogen-activated protein kinase homologues, termed CSBPs. Binding of the pyridinyl-imidazole compounds inhibited CSBP kinase activity and could be directly correlated with their ability to inhibit cytokine production, suggesting that the CSBPs are critical for cytokine production.


Subject(s)
Calcium-Calmodulin-Dependent Protein Kinases/metabolism , Cytokines/biosynthesis , Inflammation Mediators , Mitogen-Activated Protein Kinases , Amino Acid Sequence , Base Sequence , Calcium-Calmodulin-Dependent Protein Kinases/genetics , Cell Line , Chromosomes, Human, Pair 6 , Cloning, Molecular , Cytokines/antagonists & inhibitors , DNA, Complementary , Humans , Imidazoles/pharmacology , Interleukin-1/biosynthesis , Molecular Sequence Data , Monocytes/drug effects , Monocytes/metabolism , Peptide Fragments , Pyridines/pharmacology , Radioligand Assay , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Tumor Necrosis Factor-alpha/biosynthesis , p38 Mitogen-Activated Protein Kinases
18.
Peptides ; 14(4): 713-6, 1993.
Article in English | MEDLINE | ID: mdl-8234014

ABSTRACT

C-type natriuretic peptide (CNP) was measured in the hypothalamus and pituitary of four sheep by radioimmunoassay after extraction. The mean concentration of CNP in the hypothalamus was 1.01 +/- 0.08 pmol/g and 45.8 +/- 12.8 pmol/g in the pituitary. Analysis of these extracts by size exclusion HPLC showed the presence of two immunoreactive CNP components that cochromatographed with porcine CNP-53 and CNP-22 standards. Similar amounts of CNP-53- and CNP-22-like IR-CNP were present in the ovine hypothalamus (ratio 0.9:1), whereas in the pituitary, the bulk of the immunoreactive CNP was in the CNP-53-like form. These results show major differences in the distribution of IR-CNP forms between the hypothalamus and pituitary, which may reflect differences in CNP prohormone processing in these two tissues.


Subject(s)
Atrial Natriuretic Factor/analysis , Hypothalamus/chemistry , Nerve Tissue Proteins/analysis , Pituitary Gland/chemistry , Sheep/metabolism , Animals , Chromatography, High Pressure Liquid , Natriuretic Peptide, C-Type , Organ Specificity/physiology , Radioimmunoassay
20.
Am J Clin Hypn ; 35(2): 119-28, 1992 Oct.
Article in English | MEDLINE | ID: mdl-1442643

ABSTRACT

We studied 32 coronary bypass patients to examine the effect of hypnosis on recovery from surgery. The patients were assessed for hypnotizability with the Hypnotic Induction Profile (HIP) and assigned to experimental groups with a random stratification procedure to equate for differences in hypnotizability, age, and severity of illness. We taught patients in groups one and two formal hypnosis with different treatment strategies; patients in group three were not taught formal hypnosis or a treatment strategy. Scores on the HIP were significant predictors of recovery, independent of experimental treatment with formal hypnosis. Patients who scored "Midrange" stabilized more quickly in the intensive care unit (ICU) than those who scored "High" or "Low" (p = < .05). Patients who scored "High" had more labile blood pressure in the ICU compared to the "Midrange" and "Lows" (p = < .05). Measured hypnotizability was associated with the recovery sequence from surgery.


Subject(s)
Coronary Artery Bypass/psychology , Hypnosis/methods , Postoperative Complications/psychology , Sick Role , Female , Follow-Up Studies , Humans , Length of Stay , Male , Middle Aged
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