Identifying raphé respiratory chemosensory amplifiers in situ.

Activity of CO2–stimulated rat medullary raphé RCA interneurons is mediated by intra-network inputs from serotonergic and GABAergic neurons.This work was supported by NIH 2U54NS041069-06A1 from the National Institute of Neurological Disorders and Stroke (NINDS) office of Special Programs in Diversity; Alaska INBRE 5P20RR016466 from the National Center for Research Resources (NCRR); and the Institute of Arctic Biology, University of Alaska Fairbanks

CHARACTERIZATION AND TARGETING OF THE ENDOCANNABINOID SYSTEM IN TRAUMATIC BRAIN INJURY

Traumatic Brain Injuries (TBI) are considered one of the leading causes of death and disability worldwide. One emerging area of TBI research is the involvement of the endocannabinoid system (ECS) in response to brain injury. The ECS is modulated by exogenous cannabinoids such as ∆9-tetrahydrocannabinol (THC) found in Cannabis sativa. THC is a partial agonist of both cannabinoid receptors CB1R and CB2R. CB1R activation is associated with neuroprotective effects and contributes to analgesia and anxiolytic effects, whereas CB2R activation reduces inflammation. Therefore, the treatment of rats subjected to TBI with THC post-injury may restore motor function and improve behavioral profiles of injured rats. In order to assess behavioral and physiological changes associated with TBI following a closed head impact injury in a rat model, two experiments were performed. Rats were subjected to a closed-head injury impact equivalent to a mild/moderate TBI, or sham injury, and subsequently treated with THC or vehicle treatment. In the first experiment, 9 rats of both sexes were randomly assigned to: 1) SHAM TBI + Vehicle; 2) SHAM TBI + 1 mg/kg THC; 3) TBI + Vehicle; or 4) TBI + 1 mg/kg THC. Rats were subjected to a number of behavioural measures to assess drug effect, anxiety, working memory, and locomotor function following injury. Rats were assessed prior to TBI to establish a baseline, and on the above measures for 7 days following TBI. In the second experiment, 3 rats of both sexes were randomly assigned to 1) TBI + Vehicle or 2) TBI + 10mg/kg THC and tested for locomotor performance only. According to the data collected, TBI significant decreased male but not female locomotor recovery on the rotarod. Additionally, 1 mg/kg THC administration 1 h post-TBI significantly decreased male Sham-TBI, but not female locomotor activity. In the second experiment, visible differences in locomotor recovery were seen between TBI-VEH vs. TBI+THC 10 mg/kg on day 1-4 following TBI and drug administration, but according to the data collected, 10 mg/kg THC administration 1 h post-TBI did not significantly impact locomotor recovery post injury. THC or TBI did not significantly change other behavioural measures collected. These data demonstrate the importance of exploring the therapeutic potential of cannabinoids such as THC following TBI, which could contribute to reducing the longevity of lasting post-injury symptomology

Karakteristik Habitat Perkembangbiakan Vektor Filariasis Di Kecamatan Kodi Balaghar Kabupaten Sumba Barat Daya

Subdistrict scores balaghar is on filariasis endemic areas in the shouthwest district Sumba. Filariasis (elephantiasis) is a chronic infectious disease caused by the filarial worm that attacks the lymph channels and lymph (lymphatic system) that can cause acuteor chronic clinical symptoms and is transmitted by mosquitoes Mansonia, Anopheles, Culex, Amigeres. The purpose researchis to describe the characteristics of the environment and behavior to the incidence on filariasis in District Kodi Balaghar South western Sumba. This research is descriptive study with cross sectional approach that describes the spread of filariasis. Kodi was conducted in Southwest Sumba Regency Balaghar for eight months from April to November 2014. Foundas apotential habitat forlas mosquito breeding habitats where dominant is a puddle of water, springs, drains and small stream swith temperatures ranging from21-350C, from 0,22 to 795 luxillumination, range pH between7,2 to 7,7, 0-0.1‰ salinity with elevation ranging from 25-117m/asl. Where is thespecies found in the breeding habitat on is An.vagus, An.barbirostris, An.annularis, Cx.vishnui, Cx.bitaeniorhynchus, Cx.quinquefasciatus, Ar. Kuchingensis

Pengetahuan, Sikap, dan Tindakan Masyarakat tentang Filariasis Limfatik di Kecamatan Kodi Balaghar, Kabupaten Sumba Barat Daya

Kaki gajah (elephenthiasis) adalah penyakit menular menahun disebabkan oleh cacing filaria (Mikrofilaria) yang ditularkan oleh beberapa jenis nyamuk. Secara umum penyakit ini dikenal dengan sebutan filariasis. Kabupaten Sumba Barat Daya dinyatakan sebagai daerah endemis filariasis sebab ditemukan mikrofilaria rate diatas 1%. Tujuan penelitian adalah untuk mengetahui hubungan antara pengetahun, sikap, dan tindakan penderita (responden positif mikrofilaria) dan yang bukan penderita (responden negatif mikrofilaria) dengan kejadian filariasis. Penelitian dilakukan di Kecamatan Kodi Balaghar Kabupaten Sumba Barat Daya selama delapan bulan sejak bulan April hingga November 2014 menggunakan desain penelitian potong lintang. Penentuan sampel dilakukan secara purposive sampling, analisis data menggunakan uji statistik chi-square (Univariat dan bivariat). Hasil penelitian menunjukkan penderita filariasis ditemukan pada responden dengan tingkat pendidikan rendah atau tidak pernah sekolah, berusia 30‒45 tahun dan pekerjaan utama petani. Hasil uji statistik diperoleh P-value = 0,000 artinya ada hubungan yang signifikan antara tingkat pengetahuan, sikap, dan tindakan dengan kejadian positif filariasis. Hasil analisis variabel Pengetahuan diperoleh bahwa nilai Relative Risk (RR) = 6,000,artinya penderita dengan pengetahuan rendah berpeluang 6,000 kali untuk terinfeksi filariasis dibandingkan dengan responden dengan tingkat pengetahuan tinggi. Variabel Sikap diperoleh RR = 3,333 artinya penderita dengan sikap negatif berpeluang 3,333 kali untuk terinfeksi filariasis dibandingkan dengan responden dengan bersikap positif. Variabel tindakan responden diperoleh nilai RR = 1,824 artinya penderita dengan tindakan salah berpeluang 1,824 kali untuk terinfeksi filariasis dibandingkan dengan responden dengan tindakan benar. Kesimpulan, responden positif filariasis memiliki tingkat pendidikan dan pengetahuan yang lebih rendah serta memiliki sikap dan tindakan negatif terhadap upaya pengendalian faktor risiko penularan dan melakukan tindakan yang salah dalam pencegahan penyakit dibandingkan dengan responden yang bukan penderita

Gambaran Peningkatan Kadar Inter Leukin-10 (IL-10) Dan Tumor Necrosis Faktor – Alfa (TNF-α) Dengan Gejala Klinis Pada Penderita Malaria

Malaria parasites develop in erythrocytes and naturally-acquired immune responses can result in either the elimination of the parasites or a persistent response. The cytokines are responsible for all the symptoms, pathological alterations and the outcome of the infection depending on the reciprocal regulation of the pro inflammatory (TNF-α) and anti-inflammatory (IL-10) cytokines. The aim of this study was to describe the level of IL-10 and TNF- α on malaria infection, using an analytic laboratory cross-sectional design. The serum levels of the cytokines TNF- α and IL-10 from 50 patients were evaluated by indirect ELISA. The results revealed that increased levels of IL-10 and TNF-α among respondents without clinical symptoms of malaria were higher compared to respondents with clinical symptoms of P. falciparum and P. vivax. Statistically, there was no significant association between clinical symptoms with increased cytokine IL-10 and TNF-α.The ratio of TNF-α / IL-10 in respondents with clinical symptoms and without clinical symptoms indicated that the respondent without clinical symptoms was higher than that of clinical symptoms. The study concluded that molecular basis of immune response of patients in the study site is still very good because of reciprocal response between pro-inflammatory cytokines and anti-inflammatory

Penentuan Nyamuk Anopheles spp sebagai Vektor Filariasis di Kabupaten Sumba Timur dan Sumba Barat Provinsi Nusa Tenggara Timur

Abstract Filariasis is one of the neglected vector diseases and is still a problem in Indonesia. Reported from two districts in NTT Province, namely in East Sumba Regency there were 22 chronic cases and in Southwest Sumba Regency, the finger blood survey results in 2013 had an mf rate of 4.2%. The purpose of this study was to determine which Anopheles species act as vectors and obtain bionomic information from these vector species. Using the Human landing collection method, thoracic surgery and mosquito probosis. In addition, a larval breeding habitat survey was also carried out and measurements of the physical state of the Anopheles larvae breeding environment in the study area. The results of the study were obtained by An mosquitoes. vagus positively contains stage 3 filaria larvae in East Sumba Regency while in Southwest Sumba is An. sundaicus. Biting density per person per night (MBR) An. vagus of 2.8 individuals / person while the bite density of An sundaicus is 3 individuals / person. Biting and resting behavior of these two species tended to be exophagic with two peaks of biting density namely midnight and early morning. An Larva. vagus is found in buffalo and rice fields while An larvae. sundaicus is found in swamps, wells, puddles and stalls. The physical environmental factors of each habitat of the two species are generally the same, namely temperatures ranging from 26-28 0C, pH 6-8, water tends to be quiet and all habitats exposed to direct sunlight. The difference in the physical environmental factors of the habitat of these two species is only in the concentration of water salinity, which is all An habitat. vagus is 0 ‰ while An. sundaicus ranges from 3-5 ‰ Abstrak Filariasis merupakan salah satu penyakit tular vektor yang pernah terabaikan dan hingga kini masih menjadi masalah di Indonesia. Dilaporkan dari dua kabupaten di Provinsi Nusa Tenggara Timur, yaitu di Kabupaten Sumba Timur terdapat 22 kasus kronis dan di Kabupaten Sumba Barat Daya, hasil survei darah jari pada tahun 2013 didapatkan mf rate sebesar 4,2%. Tujuan penelitian ini adalah untuk menentukan spesies Anopheles apa yang berperan sebagai vektor serta mendapatkan informasi bionomik dari spesies vektor tersebut. Menggunakan metode Human landing collection, pembedahan toraks dan probosis nyamuk Selain itu juga dilakukan survei habitat perkembangbiakan larva serta pengukuran keadaan fisik lingkungan habitat perkembangbiakan larva Anopheles di wilayah penelitian. Hasil penelitian diperoleh nyamuk An. vagus positif mengandung larva stadium 3 filaria di Kabupaten Sumba Timur sedangkan di Sumba Barat Daya adalah An. sundaicus. Kepadatan mengigit per orang per malam (MBR) An. vagus sebesar 2,8 ekor/orang sedangkan kepadatan menggigit An. sundaicus sebesar 3 ekor/orang. Perilaku mengigit dan istirahat kedua spesies ini cenderung eksofagik dengan dua puncak kepadatan mengigit yaitu tengah malam dan menjelang pagi. Larva An. vagus ditemukan pada kubangan kerbau dan sawah sedangkan larva An. sundaicus ditemukan di rawa, sumur, genangan dan kobakan. Faktor fisik lingkungan masingmasing habitat kedua spesies tersebut pada umumnya sama yaitu suhu berkisar 26-28 C, pH 6-8, air cenderung diam dan semua habitat terpapar matahari langsung. Perbedaan faktor fisik lingkungan habitat kedua spesies ini adalah hanya pada konsentrasi salinitas air yaitu semua habitat An. vagus adalah 0 ‰ sedangkan An. sundaicus berkisar 3-5‰

Acute fatal presentation of ornithine transcarbamylase deficiency in a previously healthy male

Ornithine transcarbamylase (OTC) deficiency is an X-linked urea cycle defect. While hemizygous males typically present with hyperammonemic coma in infancy, reports of rare late-onset presentations exist, with poor outcomes in males up to 58 years old. Relatives with mutations identical to affected patients often remain asymptomatic, and it is likely that environmental and genetic factors influence disease penetrance and expression. Here, we present our investigation of a patient with late-onset presentation, and we emphasize the potential role of environmental and genetic factors on disease expression. The patient was a previously healthy 62-year-old man who developed mental slowing, refractory seizures, and coma over an 8-day period. Interestingly, the patient had recently used home gardening fertilizers and pesticides. Evaluations for drug and alcohol use, infections, and liver disease were negative. Despite aggressive therapy, blood NH3 concentration peaked at 2,050 μM and the patient died from cerebral edema and cerebellar herniation. Analysis of the OTC gene showed a Pro-225-Thr (P225T) change in exon 7, a mutation that has been previously implicated in OTC deficiency. This case illustrates that OTC deficiency can cause acute, severe hyperammonemia in a previously healthy adult and that the P225T mutation can be associated with late-onset OTC deficiency. We speculate that exposure to organic chemicals might have contributed to the onset of symptoms in this patient. This case also emphasizes that persistent hyperammonemia may cause irreversible neurologic damage and that after the diagnosis of hyperammonemia is established in an acutely ill patient, certain diagnostic tests should be performed to differentiate between urea cycle disorders and other causes of hyperammonemic encephalopathy

Proton Magnetic Resonance Spectroscopic Changes of the Primary Motor Cortex and Supplementary Motor Area in Hemiparetic Patients with Corticospinal Tract Injury due to Deep Intracerebral Hematoma

This study was conducted to investigate the metabolic changes in the motor and motor association cortices following axonal injury in the internal capsule that was caused by deep intracerebral hematoma. Using proton magnetic resonance spectroscopy (1H MRS), the authors studied the primary motor cortices (M-1) and sup-plementary motor areas (SMA) of 9 hemiparetic patients with documentable hemi-paresis of varying severity, and we studied 10 normal volunteers as controls. To measure the M-1 and SMA biochemical changes, 4 separate single volumes of inter-est(VOIs) were located bilaterally in the affected and unaffected hemisphere (AH and UH). 1H MRS provided a neuronal and axonal viability index by measuring levels of N-acetylaspartate (NAA) and creatine/phosphocreatine (Cr). The M-1/SMA NAA/Cr ratios of the AH and UH in patients, and the AH and normal volunteers were com-pared. The NAA/Cr ratios of the M-1 and SMA in AH, and the SMA in UH were sig-nificantly lower than those of normal volunteers. These 1H MRS findings indicate that axonal injury in the descending motor pathway at the level of internal capsule could induce metabolic changes in the higher centers of the motor pathway

Free and nonprotein amino acids of Tetrahymena pyriformis

Paper chromatography was used to determine 20 amino acids and related compounds present in both the free and the nonprotein forms in Tetrahymena pyriformis. The most abundant free amino acids in the cells were found to be glutamic acid, alanine, leucine-isoleucine, glycine, arginine, and lysine. Free methionine, cystine, and tryptophan were present in the smallest quantities. A relatively large proportion of aspartic acid, glycine, and glutamic acid was found in the conjugated form, while nearly all nonprotein arginine and lysine occurred in the free form. In line with values observed in other invertebrates and microorganisms, the [alpha]-amino nitrogen present in the free and the nonprotein forms constituted as high as a fifth and a fourth, respectively, of the total nitrogen of the protozoan cells.A fairly constant ratio of the amino acid content of the whole cell to that of the cellular protein was obtained, which indicated that the amino acid composition of the whole cell reflects that of the cellular protein.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/32514/1/0000605.pd

MRGD, a MAS-related G-protein Coupled Receptor, Promotes Tumorigenisis and Is Highly Expressed in Lung Cancer

To elucidate the function of MAS-related GPCR, member D (MRGD) in cancers, we investigated the in vitro and in vivo oncogenic function of MRGD using murine fibroblast cell line NIH3T3 in which MRGD is stably expressed. The expression pattern of MRGD in clinical samples was also analyzed. We found that overexpression of MRGD in NIH3T3 induced focus formation and multi-cellular spheroid formation, and promoted tumors in nude mice. In other words, overexpression of MRGD in NIH3T3 induced the loss of contact inhibition, anchorage-independent growth and in vivo tumorigenesis. Furthermore, it was found that the ligand of MRGD, beta-alanine, enhanced spheroid formation in MRGD-expressing NIH3T3 cells. From investigation of clinical cancer tissues, we found high expression of MRGD in several lung cancers by immunohistochemistry as well as real time PCR. Based on these results, MRGD could be involved in tumorigenesis and could also be a novel anticancer drug target