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Groundwater is the fundamental component of the hydrological system that acts as a major factor in comprehensions of the physical processes in both the land surface and the atmosphere. Determining groundwater, which directly affects the agricultural productivity of semi-arid mountainous regions, is crucial. Mountain ecosystems, once abundant with flowing water, now face immense pressure from a changing climate, evident in the drying of springs and the diminishing flow of groundwater. Ensuring a steady flow of water, fair access to it, and responsible use are the cornerstones of a secure future for mountain communities. This study aims to assess the groundwater potential zones using remote sensing and a geospatial approach in the Mustang Valley's rural municipalities (Thasang and Gharapjhong). Nine factors were assigned to assess the groundwater potential map: slope, drainage density, lineament density, geology, soil, land use/land cover, rainfall, aspect, and soil moisture. The Bayesian weights of evidence model was used to delineate the groundwater potential zone. The study categorized groundwater potential across the region, creating five zones: very high, high, moderate, low, and very low. These zones covered 0.6 %, 12.4 %, 51.2 %, 35.5 %, and 0.3 % of the study area. The accuracy of the groundwater potential map was assessed by comparing its predictions with the actual locations of springs, using the area under the curve metric. The receiver operating characteristics curve analysis yielded an area under the curve of 0.7226, indicating a 72.26 % accuracy in predicting the presence of groundwater. The findings of this paper contribute to a better understanding of groundwater potential zones, which can support policymakers and planners for hydrological, meteorological, and crop planning applications in this climatically vulnerable region.
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Optic disc pit maculopathy (ODP-M) is a rare complication of optic disc pit which can cause irreversible visual impairment. The aim of this study is to evaluate the anatomical and functional outcomes and pattern of resolution of ODP-M following vitrectomy with posterior vitreous detachment (PVD) induction and scleral tissue plug for treatment of ODP-M without ILM peeling, laser or use of long term gas/tamponade or head positioning. This retrospective study included 7 patients with ODP-M, meeting the inclusion criteria. Patients were followed up for 6 months. Complete anatomical success was defined as "Total resolution of all the fluid in retinal compartments". All of the patients had complete resolution of the optic pit maculopathy following surgery. The mean duration for complete resolution was 18.3 weeks. Pattern of resolution of ODP-M was found to be resolution of the subretinal fluid (SRF) followed by disappearance of the retinoschitic lesions (RL) and finally disappearance of macular edema (ME). The proposed minimally invasive procedure (MIP) can produce comparably good and equally reliable results for the treatment of ODP-M.
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Anomalías del Ojo , Degeneración Macular , Disco Óptico , Enfermedades de la Retina , Humanos , Vitrectomía , Estudios Retrospectivos , Procedimientos Quirúrgicos Mínimamente InvasivosRESUMEN
Frosted branched angiitis (FBA) is characteristic florid translucent retinal perivascular sheathing of both arterioles and venules in association with variable uveitis and vasculitis affecting the entire retina. The vascular sheathing is supposed to be an immune-mediated reaction, possibly due to immune complex deposition in vessel walls secondary to various underlying etiologies. The authors aim to report a case of FBA secondary to herpes simplex virus and Toxoplasma gondii infection causing the diagnostic dilemma. This is the first case report on FBA from Nepal. Case report: An 18-year-old young boy hospitalized with the diagnosis of acute viral meningo-encephalitis presented with the complaint of diminution of vision and floaters in both eyes for a week. Herpetic infection was confirmed with the cerebro-spinal fluid analysis and was under antiviral drugs. His presenting visual acuity was 20/80 in both eyes and ocular features were suggestive of FBA. The vitreous sample analysis revealed raised toxoplasma titre so intravitreal clindamycin was administered twice. The ocular features resolved in the subsequent follow ups with intravenous antiviral treatment and intravitreal antitoxoplasma treatment. Conclusions: FBA is a very rare clinical syndrome secondary to many immunological or pathological causes. So, possible etiologies must be ruled out for timely management and good visual prognosis.
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Liver impairment has been reported as a common clinical manifestation in patients with Severe Acute Respiratory Syndrome Coronavirus 2 infection, with varying degrees of severity ranging from a mild elevation of liver enzymes to acute liver failure. However, the prevalence and clinical significance of liver injury in Coronavirus Disease 2019 (COVID-19) patients, particularly in low- and middle-income countries such as Nepal, remains poorly understood. To investigate the hepatic injury related to this disease and its clinical significance, the authors conducted a retrospective study that included adult patients with COVID-19 infection in security hospitals of Nepal. Methodology: The authors performed a retrospective chart review on 1007 COVID-19-positive patients who underwent a liver function test during their admission in two COVID-19 dedicated hospitals in Nepal from April 2021 to January 2022. The data were collected and entered into Microsoft Excel before being exported to SPSS version 24 for analysis. Univariate and multivariate logistic regression were used to determine factors associated with liver injury. We reported adjusted odds ratios (aOR) with 95% CI. Results: Of the total, 549 (54.5%) patients had an acute liver injury. Among 549 patients, 68.1% were mild, 27.9% were moderate, and 5.0% were severe. Out of 1007 patients, 1.4% had cholestatic liver injury. Most patients with mild, moderate, and severe liver injury had greater than or equal to 10 C-reactive proteins (CRP). In multivariate logistic regression, sex, and CRP were significantly associated with the presence of liver injury. Males had 1.78 times higher odds of having a liver injury compared to females (aOR:1.78; 95% CI: 1.37-2.30, P-value:<0.001). Similarly, patients who had CRP greater than 10 had higher odds of having liver injury compared to those who had CRP less than 10 (aOR: 1.84; 95% CI: 1.41-2.39; P-value: <0.001). Conclusions: The present study reveals that COVID-19 infection is commonly associated with mild increased liver enzymes. However, the likelihood of developing acute liver injury was found to be higher in patients with an inflammatory state indicated by CRP levels greater than 10. Furthermore, the study highlights the sex-based difference in the prevalence of liver injury, with males demonstrating a higher predisposition.
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Children who experience violence are more prone to develop high-risk behaviour, mental illness and anxiety disorder. Nepalese law is against any form of physical violence but corporal punishment by parents on children continues in patriarchal Nepalese society. We describe a case of a young boy who attempted suicide twice due to maltreatment and discuss the legal and social issues involved.
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Regional anesthesia can be a very safe option in patients with limb girdle muscular dystrophy undergoing lower abdominal surgeries as general anesthesia and volatile anesthetic agents are associated with increased risk of malignant hyperthermia and rhabdomyolysis.
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BACKGROUND: The Asiatic wild water buffalo (Bubalus arnee) is an endangered species that is conserved in the Koshi Tappu Wildlife Reserve (KTWR), Nepal, and was recently translocated to the Chitwan National Park (CNP). Gastrointestinal (GI) parasites are the cause of significant negative health and production impacts on animals worldwide. METHODS: A coprological survey of GI parasites of wild water buffalo was carried out in the CNP in 2020. Fresh dung samples (n = 25) were collected from wild water buffaloes and analysed using sedimentation and flotation techniques for morphological identification of parasite cysts, oocysts and eggs. RESULTS: Nine different GI parasites were recorded of which Entamoeba spp. (20 samples, 80%) were the most common. The presence of Entamoeba spp. was further validated using polymerase chain reaction (PCR) analysis and DNA sequencing. The PCR results were positive for all of the microscopically positive samples, and the species was identified as Entamoeba bovis. Three samples were sequenced and formed a cluster of E. bovis, which was separated from other Entamoeba spp. in phylogenetic analysis. CONCLUSION: This is the first report for molecular detection of E. bovis from wild water buffaloes in Nepal. Future work should focus on the prevalence of such infections in water buffaloes in forest environments.
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Entamoeba , Parasitosis Intestinales , Animales , Búfalos , Entamoeba/genética , Parasitosis Intestinales/veterinaria , Nepal/epidemiología , Filogenia , Reacción en Cadena de la Polimerasa/veterinariaRESUMEN
PURPOSE: To introduce a novel tool to investigate the correlation between concomitant injuries and primary open globe injury (OGI) in the setting of ophthalmic trauma, the "Ophthalmic Trauma Correlation Matrix" (OTCM). METHODS: Retrospective cohort review, performed at a tertiary referral eye care center in Eastern Nepal, involving all eyes with OGI meeting the inclusion criteria from 2015-2018. Clinical data including details of primary injury, concurrent injuries, and clinical course were noted from hospital medical records. A correlation matrix chart was devised using matrix correlation and Pearson's correlation coefficient. This chart was then used to evaluate the association of the various injuries in the setting of OGI. RESULTS: A total of 109 eyes with OGI were included. Majority of the eyes (78, 71.6%) had zone I injuries, while most of the eyes (66, 60.6%) had penetrating injury. The most frequent concomitant injuries in all zones of OGI were traumatic lens injury (77, 70.64%), followed by hyphema (48, 44.03%), and vitreous hemorrhage (35, 32.11%). The most common concomitant injury associated with zone I was hyphema (0.873), while traumatic subluxation/cataract (0.894) and vitreous hemorrhage (0.972) were commonly associated with zone II and III, respectively. CONCLUSIONS: OTCM could be a useful tool to manage injuries related to the primary ocular injury. This additional information will aid in the prognostication, planning, and management of OGI and potentially prevent repeat surgeries and inadequate treatments.
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Catarata , Lesiones Oculares Penetrantes , Lesiones Oculares , Catarata/complicaciones , Lesiones Oculares/complicaciones , Lesiones Oculares/diagnóstico , Lesiones Oculares/epidemiología , Lesiones Oculares Penetrantes/complicaciones , Lesiones Oculares Penetrantes/diagnóstico , Lesiones Oculares Penetrantes/epidemiología , Humanos , Hipema/complicaciones , Pronóstico , Estudios Retrospectivos , Agudeza Visual , Hemorragia VítreaRESUMEN
BACKGROUND: Mortality resulting from the metastasis of retinoblastoma is uncommon in the developed world, however it still constitutes a major problem in developing countries like Nepal. The cases of retinoblastoma with increased risk of metastasis even after enucleation can be predicted from the histopathological examination of the enucleated specimen. We conducted this study aiming to assess the frequency and spectrum of high-risk histological features in enucleated specimens of retinoblastoma. MATERIALS AND METHODS: Forty-two specimens of primary enucleation done for treatment of retinoblastoma received in the Department of Pathology at UCMS from 1st January 2016 to 31st December 2018 were included in the study. All slides were reviewed for high-risk histological features along with tumor differentiation, tumor extension, necrosis, and staging. Correlation of high-risk histological features with age and tumor size was calculated using unpaired t-test and correlation with tumor differentiation, necrosis and staging was done using Pearson Chi square test. RESULTS: The median age at enucleation was 24 months. All patients had endophytic lesion with a mean tumor size of 1.8cm. One or more high-risk histological features were identified in 30.9% (13/42). The most common high-risk histological feature was retrolaminar optic nerve invasion (10/12, 71.4%). Statistically significant correlation of high risk histological features was noted with tumor size (p=0.011) and AJCC stage of tumor (p=0.0001). CONCLUSION: Complete histopathological evaluation of retinoblastoma requires searching for high-risk histological features, the presence of which will guide the clinician in timely planning for subsequent neoadjuvant therapy.
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Neoplasias de la Retina , Retinoblastoma , Enucleación del Ojo , Humanos , Lactante , Nepal/epidemiología , Neoplasias de la Retina/diagnóstico , Neoplasias de la Retina/epidemiología , Neoplasias de la Retina/cirugía , Retinoblastoma/diagnóstico , Retinoblastoma/epidemiología , Retinoblastoma/cirugía , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Open globe injury (OGI) is one of the most devastating form of ocular trauma. The aim of the study is to identify the epidemiology and predict visual outcomes in traumatic open globe injuries using ocular trauma score (OTS) and correlate with final visual acuity (VA) at 3 months. METHODS: Patients older than 5 years, presenting to B.P. Koirala Lions Centre for Ophthalmic Studies (BPKLCOS) from March 2016- March 2017 with OGI that met inclusion criteria were evaluated. Patient profile, nature and cause of injury, and time to presentation were recorded. Patients were managed accordingly and followed up to 3 months. An OTS score for each patient was calculated and raw scores were categorized accordingly. The VA after 3 months were compared to the predicted OTS values. RESULTS: Seventy-three eyes of 72 patients were examined. 76 % were male, and the mean age was 26.17 years (median, 23.5 years). The mean time from injury to presentation was < 6 hours (30 patients, 41 %). Thirty-seven eyes (51 %) had zone I trauma, followed by twenty eyes (27 %) with zone II, and sixteen eyes (22 %) with zone III trauma. Sixty-five patients (90 %) were managed surgically, and fifty (68 %) received intravitreal antibiotics with steroid. When compared, the projected VA as per OTS were able to predict actual final visual outcomes in 60 % of the eyes with OGI of various zones. CONCLUSIONS: OTS can be an accurate predictive tool for final visual acuity even with a short follow up period of 3 months; with poor presenting visual acuity, delayed presentation, posterior zones of injury, need for intravitreal injections, endophthalmitis, and globe rupture associated with poorer prognosis.
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Lesiones Oculares Penetrantes , Lesiones Oculares , Adulto , Lesiones Oculares/diagnóstico , Lesiones Oculares/epidemiología , Lesiones Oculares Penetrantes/diagnóstico , Lesiones Oculares Penetrantes/epidemiología , Femenino , Humanos , Masculino , Pronóstico , Estudios Retrospectivos , Índices de Gravedad del Trauma , Agudeza VisualRESUMEN
Intravitreal steroid implants are the latest trend for uveitis macular oedema treatment. Dexamethasone intravitreal implants are new in our contexts but we report 2 cases of uveitic cystoid macular oedema where this implant proved very useful in the treatment of recalcitrant macular oedema where other treatment modality fails. Two cases of non-infectious uveitis and intermediate uveitis with recalcitrant uveitic macular oedema underwent dexamethasone intravitreal implantation. Their central macular thickness and central macular volume reduced significantly with the implant. With the reduction in macular parameters, the best-corrected visual acuity also improved and visual rehabilitation was achieved. Thus, dexamethasone intravitreal implant helps in sustained drug delivery inside the vitreous leading to resolution of uveitic macular oedema in recalcitrant cases. Keywords: Macular oedema; ozurdex; steroid; uveitis; vision.
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Edema Macular , Uveítis , Dexametasona/uso terapéutico , Implantes de Medicamentos/uso terapéutico , Glucocorticoides/uso terapéutico , Humanos , Inyecciones Intravítreas , Edema Macular/tratamiento farmacológico , Nepal , Estudios Retrospectivos , Resultado del Tratamiento , Uveítis/tratamiento farmacológico , Agudeza VisualRESUMEN
BACKGROUND: The factors that predispose to pulmonary tuberculosis (PTB) are not fully understood. Previous studies have shown that cytokine gene polymorphisms were associated with PTB. OBJECTIVES: In this study, we have investigated the relationship between ILB, IL6, and TNFα polymorphisms and a predisposition to Mycobacterium tuberculosis (MTB) infection and PTB. METHODS: A total of 209 cases of PTB, 201 subjects with latent TB infection (LTBI), and 204 healthy controls (HCS) were included in this study. Logistic regression analyses under allelic, homozygous, and heterozygous models were used to calculate P values, odds ratios (ORs), and 95% confidence intervals (CIs) for assessing the association between single nucleotide polymorphisms (SNPs) and disease risk, adjusting for sex and age. Genotyping was conducted using the improved multiplex ligase detection reaction (iMLDR) method. RESULTS: When comparing PTB patients with LTBI subjects, significant associations with disease development were observed for SNPs of IL6 and TNFα. When comparing LTBI subjects with HCS, IL1B polymorphisms were significantly associated with LIBI. Haplotype analyses suggested that the CGG haplotype of IL1B was associated with an increased risk of PTB (P = 0.039, OR = 1.34, 95% CI: 1.01-1.76), while the TTGCG haplotype of TNFα was a protective factor against PTB (P = 0.039, OR = 0.66, 95% CI: 0.44-0.98). CONCLUSION: Our study demonstrated that IL1B variants were related to LTBI and IL6 and TNFα variants were associated with PTB.
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Pueblo Asiatico , Interleucina-1beta/genética , Interleucina-6/genética , Polimorfismo de Nucleótido Simple , Tuberculosis Pulmonar , Factor de Necrosis Tumoral alfa/genética , Pueblo Asiatico/etnología , Pueblo Asiatico/genética , China/etnología , Femenino , Haplotipos , Humanos , Masculino , Tuberculosis Pulmonar/etnología , Tuberculosis Pulmonar/genéticaRESUMEN
RATIONALE: Studies in human and non-human primates demonstrate that social status is an important determinant of cocaine reinforcement. However, it is unclear whether social rank is associated with other traits that also predispose to addiction and whether social status similarly predicts cocaine self-administration in rats. OBJECTIVES: The objective of this study is to investigate whether social ranking assessed using a resource competition task affects (i) the acquisition, maintenance and reinstatement of cocaine self-administration; (ii) the dopaminergic markers in the striatum; and (iii) the expression of ancillary traits for addiction. METHODS: Social ranking was determined in group-housed rats based upon drinking times during competition for a highly palatable liquid. Rats were then evaluated for cocaine self-administration and cue-induced drug reinstatement or individual levels of impulsivity, anxiety and novelty-induced locomotor activity. Finally, dopamine content, dopamine transporter (DAT) and dopamine D2/D3 (D2/3) receptor binding were measured postmortem in the dorsal and ventral striatum. RESULTS: Rats deemed socially dominant showed enhanced novelty reactivity but were neither more impulsive nor anxious compared with subordinate rats. Dominant rats additionally maintained higher rates of cocaine self-administration but showed no differences in the acquisition, extinction and reinstatement of this behaviour. D2/3 binding was elevated in the nucleus accumbens shell and dorsal striatum of dominant rats when compared to subordinate rats, and was accompanied by elevated DAT and reduced dopamine content in the nucleus accumbens shell. CONCLUSIONS: These findings show that social hierarchy influences the rate of self-administered cocaine but not anxiety or impulsivity in rats. Similar to non-human primates, these effects may be mediated by striatal dopaminergic systems.
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Cocaína/administración & dosificación , Cuerpo Estriado/metabolismo , Conducta Exploratoria/efectos de los fármacos , Receptores de Dopamina D2/metabolismo , Receptores de Dopamina D3/metabolismo , Predominio Social , Animales , Conducta Adictiva/metabolismo , Cuerpo Estriado/efectos de los fármacos , Dopamina/metabolismo , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Inhibidores de Captación de Dopamina/farmacología , Conducta Exploratoria/fisiología , Masculino , Unión Proteica/fisiología , Ratas , Refuerzo en Psicología , AutoadministraciónRESUMEN
Dysfunction of the orbitofrontal cortex (OFC) impairs the ability of individuals to flexibly adapt behavior to changing stimulus-reward (S-R) contingencies. Impaired flexibility also results from interventions that alter serotonin (5-HT) and dopamine (DA) transmission in the OFC and dorsomedial striatum (DMS). However, it is unclear whether similar mechanisms underpin naturally occurring variations in behavioral flexibility. In the present study, we used a spatial-discrimination serial reversal procedure to investigate interindividual variability in behavioral flexibility in rats. We show that flexibility on this task is improved following systemic administration of the 5-HT reuptake inhibitor citalopram and by low doses of the DA reuptake inhibitor GBR12909. Rats in the upper quintile of the distribution of perseverative responses during repeated S-R reversals showed significantly reduced levels of the 5-HT metabolite, 5-hydroxy-indoleacetic acid, in the OFC. Additionally, 5-HT2A receptor binding in the OFC of mid- and high-quintile rats was significantly reduced compared with rats in the low-quintile group. These perturbations were accompanied by an increase in the expression of monoamine oxidase-A (MAO-A) and MAO-B in the lateral OFC and by a decrease in the expression of MAO-A, MAO-B, and tryptophan hydroxylase in the dorsal raphé nucleus of highly perseverative rats. We found no evidence of significant differences in markers of DA and 5-HT function in the DMS or MAO expression in the ventral tegmental area of low- vs high-perseverative rats. These findings indicate that diminished serotonergic tone in the OFC may be an endophenotype that predisposes to behavioral inflexibility and other forms of compulsive behavior.
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Discriminación en Psicología/fisiología , Núcleo Dorsal del Rafe/metabolismo , Corteza Prefrontal/metabolismo , Aprendizaje Inverso/fisiología , Serotonina/metabolismo , Percepción Espacial/fisiología , Animales , Citalopram/farmacología , Condicionamiento Operante/efectos de los fármacos , Discriminación en Psicología/efectos de los fármacos , Núcleo Dorsal del Rafe/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Expresión Génica , Masculino , Monoaminooxidasa/genética , Monoaminooxidasa/metabolismo , Piperazinas/farmacología , Corteza Prefrontal/efectos de los fármacos , Unión Proteica/efectos de los fármacos , ARN Mensajero/metabolismo , Ratas , Refuerzo en Psicología , Aprendizaje Inverso/efectos de los fármacos , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Percepción Espacial/efectos de los fármacos , Triptófano Hidroxilasa/genética , Triptófano Hidroxilasa/metabolismoRESUMEN
Accumulating evidence indicates that impulsivity, in its multiple forms, involves cortical and subcortical mechanisms and abnormal dopamine (DA) transmission. Although decreased DA D2/D3 receptor availability in the nucleus accumbens (NAcb) predicts trait-like impulsivity in rats it is unclear whether this neurochemical marker extends to both the NAcb core (NAcbC) and shell (NAcbS) and whether markers for other neurotransmitter systems implicated in impulsivity such as serotonin (5-HT), endogenous opioids and γ-amino-butyric acid (GABA) are likewise altered in impulsive rats. We therefore used autoradiography to investigate DA transporter (DAT), 5-HT transporter (5-HTT) and D1, D2/D3, µ-opioid and GABA(A) receptor binding in selected regions of the prefrontal cortex and striatum in rats expressing low and high impulsive behaviour on the five-choice serial reaction-time task. High-impulsive (HI) rats exhibited significantly lower binding for DAT and D2/D3 receptors in the NAcbS and for D1 receptors in the NAcbC compared with low-impulsive (LI) rats. HI rats also showed significantly lower GABA(A) receptor binding in the anterior cingulate cortex. For all regions where receptor binding was altered in HI rats, binding was inversely correlated with impulsive responding on task. There were no significant differences in binding for 5-HTT or µ-opioid receptors in any of the regions investigated. These results indicate that altered D2/D3 receptor binding is localised to the NAcbS of trait-like impulsive rats and is accompanied by reduced binding for DAT. Alterations in binding for D1 receptors in the NAcbC and GABA(A) receptors in the anterior cingulate cortex demonstrate additional markers and putative mechanisms underlying the expression of behavioural impulsivity.
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Cuerpo Estriado/fisiología , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Conducta Impulsiva/metabolismo , Corteza Prefrontal/fisiología , Receptores Dopaminérgicos/metabolismo , Receptores de GABA-A/metabolismo , Animales , Cuerpo Estriado/diagnóstico por imagen , Cuerpo Estriado/metabolismo , Ligandos , Masculino , Corteza Prefrontal/diagnóstico por imagen , Corteza Prefrontal/metabolismo , Unión Proteica , Cintigrafía , Ratas , Tiempo de Reacción , Proteínas de Transporte de Serotonina en la Membrana Plasmática/metabolismoRESUMEN
The serotonin-1A (5-HT(1A)) receptor is of particular interest in human positron emission tomography (PET) studies of major depressive disorder (MDD). Of the eight studies investigating this issue in the brains of patients with MDD, four reported decreased 5-HT(1A) receptor density, two reported no change, and two reported increased 5-HT(1A) receptor density. While clinical heterogeneity may have contributed to these differing results, methodological factors by themselves could also explain the discrepancies. This review highlights several of these factors, including the use of the cerebellum as a reference region and the imprecision of measuring the concentration of parent radioligand in arterial plasma, the method otherwise considered to be the 'gold standard'. Other potential confounds also exist that could restrict or unexpectedly affect the interpretation of results. For example, the radioligand may be a substrate for an efflux transporter - like P-gp - at the blood-brain barrier; furthermore, the binding of the radioligand to the receptor in various stages of cellular trafficking is unknown. Efflux transport and cellular trafficking may also be differentially expressed in patients compared to healthy subjects. We believe that, taken together, the existing disparate findings do not reliably answer the question of whether 5-HT(1A) receptors are altered in MDD or in subgroups of patients with MDD. In addition, useful meta-analysis is precluded because only one of the imaging centers acquired all the data necessary to address these methodological concerns. We recommend that in the future, individual centers acquire more thorough data capable of addressing methodological concerns, and that multiple centers collaborate to meaningfully pool their data for meta-analysis.
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Trastorno Depresivo Mayor/diagnóstico por imagen , Trastorno Depresivo Mayor/metabolismo , Tomografía de Emisión de Positrones , Receptor de Serotonina 5-HT1A/metabolismo , HumanosRESUMEN
UNLABELLED: Subcutaneous injection of endothelin-1 (ET-1) into the glabrous skin of the rat's hind paw is known to produce impulses in nociceptors and acute nocifensive behavioral responses, such as hind paw flinching, and to sensitize the skin to mechanical and thermal stimulation. In this report, we show that in contrast to the responses in glabrous skin, ET-1 injected subcutaneously into rat hairy skin causes transient antinociception. Concentrations of 1 to 50 microM ET-1 (in 0.05 mL) depress the local nocifensive response to noxious tactile probing at the injection site with von Frey filaments for 30 to 180 minutes; distant injections have no effect at this site, showing that the response is local. Selective inhibition of ET(A) but not of ET(B) receptors inhibits this antinociception, as does coinjection with nimodipine (40 muM), a blocker of L-type Ca(2+) channels. Local subcutaneous injection of epinephrine (45 microM) also causes antinociception through alpha-1 adrenoreceptors, but such receptors are not involved in the ET-1-induced effect. Both epinephrine and ET-1, at antinociceptive concentrations, reduce blood flow in the skin; the effect from ET-1 is largely prevented by subcutaneous nimodipine. These data suggest that ET-1-induced antinociception in the hairy skin of the rat involves cutaneous vasoconstriction, presumably through neural ischemia, resulting in conduction block. PERSPECTIVE: The pain-inducing effects of ET-1 have been well documented in glabrous skin of the rat, a frequently used test site. The opposite behavioral effect, antinociception, occurs from ET-1 in hairy skin and is correlated with a reduction in blood flow. Vasoactive effects are important in assessing mechanisms of peripherally acting agents.