Adult Starvation and Disease-Related Malnutrition: A Proposal for Etiology-Based Diagnosis in the Clinical Practice Setting From the International Consensus Guideline Committee

Background & Aims: Multiple definitions for malnutrition syndromes are found in the literature resulting in confusion. Recent evidence suggests that varying degrees of acute or chronic inflammation are key contributing factors in the pathophysiology of malnutrition that is associated with disease or injury. Methods: An International Guideline Committee was constituted to develop a consensus approach to defining malnutrition syndromes for adults in the clinical setting. Consensus was achieved through a series of meetings held at the ASPEN. and ESPEN Congresses. Results: It was agreed that an etiology-based approach that incorporates a current understanding of inflammatory response would be most appropriate. The Committee proposes the following nomenclature for nutrition diagnosis in adults in the clinical practice setting. ""Starvation-related malnutrition,"" when there is chronic starvation without inflammation, ""chronic disease-related malnutrition"", when inflammation is chronic and of mild to moderate degree, and ""acute disease or injury-related malnutrition"", when inflammation is acute and of severe degree. Conclusions: This commentary is intended to present a simple etiology-based construct for the diagnosis of adult malnutrition in the clinical setting. Development of associated laboratory, functional, food intake, and body weight criteria and their application to routine clinical practice will require validation. (JPEN J Parenter Enteral Mar. 2010;34:156-159)

Non-expression of insulin-like growth factor-I receptor is associated with apoptosis: an ultrastructural study on rat ameloblasts

Insulin-like growth factor-I (IGF-I) is a preiotrophic polypeptide which appears to have roles both as a circulating endocrine hormone and as a locally synthesized paracrine or autocrine tissue factor. IGF-I plays a major role in regulating the growth of cells in vivo and in vitro and initiates metabolic and mitogenic processes in a wide variety of cell types by binding to specific type I receptors in the plasma membrane, In this study, we report the distribution of IGF-I receptors in odontogenic cells at the ultrastructural level using the high resolution protein A-gold technique, In the pre-secretory stage, very little gold label was visible over the ameloblasts and odontoblasts, During the secretory stage the label was mostly seen in association with the cell membranes and endoplasmic reticulum of the ameloblasts. Lysosome-like elements in the post-secretory stage were labelled as well as multivesicular dense bodies, Very little labelling was encountered in the ameloblasts in the transitional stage, where apoptotic bodies were clearly visible, The maturation stage also exhibited labelling of the secretory-like granules in the distal surface. The presence of gold particles over the plasma membrane is an indication that IGF-I receptor is a membrane-bound receptor. Furthermore, the intracellular distribution of the label over the endoplasmic reticulum supports the local synthesis of the IGF-I receptor. The absence of labelling over the transitional ameloblasts suggests that the transitional stage may require the non-expression of IGF-I as a prerequiste or even a trigger for apoptosis.

Single nucleotide polymorphism C/T-13910, located upstream of the lactase gene, associated with adult-type hypolactasia: Validation for clinical practice

Objectives: To validate C/T-13910 polymorphism associated with primary hypolactasia for clinical practice. Design and methods: Lactose breath test and PCR-RFLP for the C/T-13910 polymorphism were performed. Results: Twenty-seven of 28 patients with genotype CC had positive breath tests, all twenty-two patients with genotypes CT or TT had negative breath tests. Agreement of tests was high (p<0.0001; Kappa Index 0.96). Conclusion: C/T-13910 polymorphism detection may be a new tool for primary hypolactasia diagnosis. (C) 2008 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Differential expression of Egr-1-like DNA-binding activities in the naive rat brain and after excitatory stimulation

Egr-1 and related proteins are inducible transcription factors within the brain recognizing the same consensus DNA sequence. Three Egr DNA-binding activities were observed in regions of the naive rat brain. Egr-1 was present in all brain regions examined. Bands composed, at least in part, of Egr-2 and Egr-3 were present in different relative amounts in the cerebral cortex, striatum, hippocampus, thalamus, and midbrain. All had similar affinity and specificity for the Egr consensus DNA recognition sequence. Administration of the convulsants NMDA, kainate, and pentylenetetrazole differentially induced Egr-1 and Egr-2/3 DNA-binding activities in the cerebral cortex, hippocampus, and cerebellum. All convulsants induced Egr-1 and Egr-2 immunoreactivity in the cerebral cortex and hippocampus. These data indicate that the members of the Egr family are regulated at different levels and may interact at promoters containing the Egr consensus sequence to fine tune a program of gene expression resulting from excitatory stimuli.

Treadmill running protects spinal cord contusion from secondary degeneration

It is known that physical activity triggers changes in the central nervous system Adult rats, trained on treadmills for 4 weeks, and a group of sedentary rats was submitted to contuse moderate spinal cord injury A group of sedentary rats was submitted to a sham operation The trained group continued running on treadmill after lesion for 4 weeks Motor behavior evaluated by BBB score was smaller in the sedentary group compared to the trained rats by 7 days after lesion Computerized activity monitor showed clear-cut differences in spontaneous motor parameters in trained rats only before lesion After surgery, sedentary rats showed changes in motor parameters but not in later periods of analysis Animals were euthanized by 28 days after surgery, and their spinal cords were processed for Nissl staining and immunohistochemistry The number of the remaining neurons and the lesion areal and lesion volume fractions were obtained by stereological method The number of the remaining neurons did not change after training Lesion volume and lesion areal fraction per section were smaller in the trained group Lesion index was more pronounced in the sedentary group Microdensitometric image analysis demonstrated a microglial reaction, astroglial activation, and glial FGF-2 production more pronounced in the spinal cord of sedentary animals GAP-43 was higher in caudal levels of contusion in the sedentary group In conclusion, treadmill running may favor a better functional recovery in the acute period after spinal cord lesion and wound repair processes leading to neuroprotection (C) 2010 Elsevier B V All rights reserved

Neuropeptide Y in Rat Spiral Ganglion Neurons and Inner Hair Cells of Organ of Corti and Effects of a Nontraumatic Acoustic Stimulation

Neuropeptide Y (NPY) is an important neuromodulator found in central and peripheral neurons. NPY was investigated in the peripheral auditory pathway of conventional housed rats and after nontraumatic sound stimulation in order to localize the molecule and also to describe its response to sound stimulus. Rats from the stimulation experiment were housed in monitored sound-proofed rooms. Stimulated animals received sound stimuli (pure tone bursts of 8 kHz, 50 ms duration presented at a rate of 2 per second) at an intensity of 80 dB sound pressure level for 1 hr per day during 7 days. After euthanizing, rat cochleae were processed for one-color immunohistochemistry. The NPY immunoreactivity was detected in inner hair cells (IHC) and also in pillar and Deiters` cells of organ of Corti, and in the spiral ganglion putative type I (1,009 m3) and type II (225 m3) neurons. Outer hair cells (OHC) showed light immunoreaction product. Quantitative microdensitometry showed strong and moderate immunoreactions in IHC and spiral ganglion neurons, respectively, without differences among cochlear turns. One week of acoustic stimulation was not able to induce changes in the NPY immunoreactivity intensity in the IHC of cochlea. However, stimulated rats showed an overall increase in the number of putative type I and type II NPY immunoreactive spiral ganglion neurons with strong, moderate, and weak immunolabeling. Localization and responses of NPY to acoustic stimulus suggest an involvement of the neuropeptide in the neuromodulation of afferent transmission in the rat peripheral auditory pathway.

Development of an animal model for endometrial ablation using trichloroacetic acid

Objective: To develop an animal model of endometrial ablation, and to evaluate the histologic effects of trichloroacetic acid (TCA) in the uterine cavity. Design: Experimental prospective. Setting: Department of gynecology. Patient(s): Thirty female adult rats. Intervention(s): Animals were submitted to injection of TCA in one uterine horn and saline solution in the other. Group 1 was sacrificed the day after the procedure. Group 2 was sacrificed in phase of diestrus. Superficial epithelia of the endometrium, stromal thickness, endometrial glands, and myometrium thickness were compared among the uterine horns of the same rats of group 1. The same evaluation was performed in group 2. Endometrial regeneration was evaluated. Main Outcome Measure(s): Histologic effects. Result(s): In group 1, histologic parameters showed endometrial destruction on TCA injected uterine horn. In group 2, four rats died after the procedure, and six rats had no viable material. In the rest of the group, TCA-injected uterine horns showed endometrial destruction. Superficial epithelia of the endometrium and stromal thickness were similar between TCA uterine horn from groups. However, the number of endometrial glands was higher in group 1. Conclusion(s): The study developed an experimental model for endometrial ablation. TCA acid is a potent agent for endometrial ablation in rat model. No endometrial regeneration was observed after recovery of cycle. (Fertil Steril (R) 2011; 95: 2418-21. (C) 2011 by American Society for Reproductive Medicine.)

A selective cyclooxygenase-2 inhibitor suppresses the growth of endometriosis with an antiangiogenic effect in a rat model

Objective: To analyze the antiangiogenic effects of the selective cyclooxygenase-2 (COX-2) inhibitor parecoxib on the growth of endometrial implants in a rat model of peritoneal endometriosis. Design: Pharmacologic interventions in an experimental model of peritoneal endometriosis. Setting: Research laboratory in the Federal University of Rio de Janeiro. Animal(s): Twenty female Sprague-Dawley rats with experimentally induced endometriosis. Intervention(s): After implantation and establishment of autologous endometrium onto the peritoneum abdominal wall, rats were randomized into groups and treated with parecoxib or the vehicle by IM injection for 30 days. Main Outcome Measure(s): Vascular density, the expression of vascular endothelial growth factor (VEGF) and its receptor Flk-1, the distribution of activated macrophages, the expression of COX-2, and the prostaglandin concentration in the endometriotic lesions treated with parecoxib were analyzed. Result(s): The treatment significantly decreased the implant size, and histologic examination indicated mostly atrophy and regression. A reduction in microvessel density and in the number of macrophages, associated with decreased expression of VEGF and Flk-1, also were observed. The treatment group showed a low concentration of prostaglandin E(2). Conclusion(s): These results suggest that the use of COX-2 selective inhibitors could be effective to suppress the establishment and growth of endometriosis, partially through their antiangiogenic activity. (Fertil Steril (R) 2010; 93: 2674-9. (C) 2010 by American Society for Reproductive Medicine.)

Characterization of bovine transcripts preferentially expressed in testis and with a putative role in spermatogenesis

Although the number of genes known to be associated with bovine spermatogenesis has increased in the past few years, regulation of this biological process remains poorly understood. Therefore, discovery of new male fertility genetic markers is of great value for assisted selection in commercially important cattle breeds, e.g., Nelore, that have delayed reproductive maturation and low fertility rates. The objective of the present study was to identify sequences associated with spermatogenesis that could be used as fertility markers. With RT-PCR, the following five transcripts preferentially expressed in adult testis were detected: TET(656) detected only in adult testis; TET(868) and TET(515) expressed preferentially in adult testis but also detected in fetal gonads of both sexes; and TET(456) and TET(262). expressed primarily in the testis, but also present in very low amounts in somatic tissues. Based on their homologies and expression profiles, we inferred that they had putative roles in spermatogenesis. Detection of sequences differentially expressed in testis, ovary, or both, was a useful approach for identifying new genes related to bovine spermatogenesis. The data reported here contributed to discovery of gene pathways involved in bovine spermatogenesis, with potential for prediction of fertility. (C) 2011 Elsevier Inc. All rights reserved.

Inhibition of phospholipase A(2) increases Tau phosphorylation at Ser214 in embryonic rat hippocampal neurons

Background: Arachidonic acid is released from cellular membranes by the action of phospholipase A(2) (PLA(2)) and is implicated in microtubule-associated protein Tau phosphorylation. Tau hyperphosphorylation affects its ability to stabilize microtubules. Objective: To determine the effect of PLA(2) inhibition on the phosphorylation state of Tau phosphoepitopes in primary cultures of hippocampal neurons. Methods: 4 DIC neurons were incubated at different concentrations of methyl-arachidonylfluorophosphonate (MAFP), an irreversible inhibitor of cPLA(2) and iPLA(2). Changes on Tau phosphorylation were determined by Western blotting with a panel of anti-Tau antibodies (C-terminal, Ser199/202, Ser202/205, Ser396 and Ser214). Results: The Ser214 site was hyperphosphorylated upon MAFP treatment. Significant differences were observed with 10 mu M (p = 0.01), 50 mu M (p = 0.01) and 100 mu M (p = 0.05) of MAFP. Less-intense changes were found in other phosphoepitopes. Conclusion: The present findings indicate that the phosphorylation of Ser214 is regulated by c- and/or iPLA(2), whereas other phosphoepitopes primarily regulated by GKS3b were not affected. (C) 2009 Elsevier Ltd. All rights reserved.

Centella asiatica water extract inhibits iPLA(2) and cPLA(2) activities in rat cerebellum

Centella asiatica (L.) Urb an is distributed widely in South America and Asia and is known as a therapeutic agent in folk medicine, capable of improving memory and treating several neurological disorders. Asiaticoside is one of the compounds found in C asiatica leaves that is suggested to be responsible for its pharmacological potential. Phospholipase A(2) (PLA(2)) is a group of enzymes that has abnormal activity in the central nervous system in some neuropsychiatric diseases. In this work, the asiaticoside present in C asiatica water extract was quantified by HPLC analysis. We also evaluated the activity of subtypes of PLA(2) in cerebellar samples from rats after C asiatica water extract treatment using a radioenzymatic assay. Asiaticoside was the major compound (84%) found in Centella water extract. We found a dose-dependent inhibitory effect of C asiatica water extract on the activity of Ca(2+)-independent PLA(2) (iPLA(2)) and cytosolic PLA(2) (cPLA(2)). The inhibition of these enzymes in the brain suggests that C asiatica may be useful to treat conditions associated with increased PLA(2) activity in the brain, such as epilepsy, stroke, multiple sclerosis and other neuropsychiatric disorders. (C) 2008 Elsevier GmbH. All rights reserved.

Lack of Association Between a 3 ` UTR VNTR Polymorphism of Dopamine Transporter Gene (SLC6A3) and ADHD in a Brazilian Sample of Adult Patients

Objective: To investigate a possible association between a 3`UTR VNTR polymorphism of the dopamine transporter gene (SLC6A3) and ADHD in a Brazilian sample of adult patients. Method: Study Case-control with 102 ADHD adult outpatients (DSM-IV criteria) and 479 healthy controls. The primers` sequence used were: 3`UTR-Forward: 5`TGT GGT GAT GGG AAC GGC CTG AG 3` and 3`UTR-Reverse: 5`CTT CCT GGA GGT CAC GGC TCA AGG 3`. Alleles of the 3`UTR were coded according to their number of repeats: 6- repeat 320 bp (allele 6), 8- repeat 400 bp (allele 8), 9-repeat 480 bp (allele 9), 10- repeat 480 bp (allele 10), and 11- repeat 520 bp (allele 11). Results: There were no allelic (chi(2) = 2.67, 5df, p = .75) and genotypic (chi(2) = 7.20, 1df, p = .61) association between adult ADHD and VNTR 3`UTR polymorphism of SLC6A3. Conclusion: Our findings do not support SLC6A3 as marker genetic susceptibility factor in adult ADHD. More comprehensive polymorphism coverage within the SLC6A3 region should be conducted in larger samples, including comparisons in clinical subgroups, and in samples with different ethnic backgrounds. (J. of Att. Dis. 2011; 15(4) 305-309)

Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure

The goal of this work was to compare the differences between human immunodeficiency Virus type 1 (HIV-1) of B and F1 Subtypes in the acquisition of major and rninot- protease inhibitor (P1)-associated resistance mutations and of other polymorphisms at the protease (PR) gene, through a cross sectional Study. PR sequences from subtypes B and F1 isolates matched according to P1 exposure time from Brazilian patients were included in this study. Sequences were separated in four groups: 24 and 90 from children and 141 and 99 from adults infected with isolates of subtypes F1 and B, respectively. For comparison, 211 subype B and 79 subtype F1 PR sequences from drug-naive individuals Were included. Demographic and clinical data were similar among B- and F1-infected patients. In untreated patients, Mutations L1OV, K20R, and M361 were more frequent in subtype F1, while L63P, A7IT, and V771 were more prevalent in Subtype B. In treated patients, K20M, D30N, G73S, 184V, and L90M, were More prevalent in subtype B, and K20T and N88S Were more prevalent in Subtype F1. A higher proportion of subtype F1 than Of subtype B Strains Containing other polymorphisms was observed. V82L mutation was Present With increased frequency in isolates from children compared to isolates from adults infected with both subtypes. We could observe a faster resistance emergence in children than in adults, during treatment with protease inhibitors. This data provided evidence that, although rates of overall drug resistance do not differ between subtypes B and F1, the former accumulates resistance at higher proportion in specific amino acid positions of protease when compared to the latter. (c) 2008 Elsevier B.V. All rights reserved.

A rodent model of NASH with cirrhosis, oval cell proliferation and hepatocellular carcinoma

Background/Aims: Hepatocellular carcinoma (HCC) is a well recognized complication of advanced NASH (non-alcoholic steatohepatitis). We sought to produce a rat model of NASH, cirrhosis and HCC. Methods: Adult Sprague-Dawley rats, weighing 250-300 g, were fed a choline-deficient, high trans-fat diet and exposed to DEN in drinking water. After 16 weeks, the animals underwent liver ultrasound (US), sacrifice and assessment by microscopy, immunohistochemistry and transmission electron microscopy (TEM). Results: US revealed steatosis and focal lesions in 6 of 7. All had steatohepatitis defined as inflammation, advanced fibrosis and ballooning with Mallory-Denk bodies (MDB) with frank cirrhosis in 6. Areas of more severe injury were associated with anti-CK19 positive ductular reaction. HCC, present in all, were macro-trabecullar or solid with polyhedral cells with foci of steatosis and ballooned cells. CK19 was positive in single or solid nests of oval cells and in neoplastic hepatocytes. TEM showed ballooning with small droplet fat, dilated endoplasmic reticulum and MDB in non-neoplastic hepatocytes and small droplet steatosis in some cancer cells. Conclusions: This model replicated many features of NASH including steatohepatitis with ballooning, fibrosis, cirrhosis and hepatocellular carcinoma. Oval cell proliferation was evident and the presence anti-CK 19 positivity in the cancer suggests oval cell origin of the malignancy. (C) 2008 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.