Simultaneous Biofortification of Wheat with Zinc, Iodine, Selenium, and Iron through Foliar Treatment of a Micronutrient Cocktail in Six Countries.

Field experiments were conducted on wheat to study the effects of foliar-applied iodine(I) alone, Zn (zinc) alone, and a micronutrient cocktail solution containing I, Zn, Se (selenium), and Fe (iron) on grain yield and grain concentrations of micronutrients. Plants were grown over 2 years in China, India, Mexico, Pakistan, South Africa, and Turkey. Grain-Zn was increased from 28.6 mg kg-1 to 46.0 mg-1 kg with Zn-spray and 47.1 mg-1 kg with micronutrient cocktail spray. Foliar-applied I and micronutrient cocktail increased grain I from 24 µg kg-1 to 361 µg kg-1 and 249 µg kg-1, respectively. Micronutrient cocktail also increased grain-Se from 90 µg kg-1 to 338 µg kg-1 in all countries. Average increase in grain-Fe by micronutrient cocktail solution was about 12%. The results obtained demonstrated that foliar application of a cocktail micronutrient solution represents an effective strategy to biofortify wheat simultaneously with Zn, I, Se and partly with Fe without yield trade-off in wheat.

Post mortem computed tomography (PMCT) guided lung biopsy: A preliminary case report.

Tuberculosis (TB) is a highly infectious disease on the rise caused by the organism Mycobacterium tuberculosis and health care workers working in emergency departments, medical wards and autopsy rooms are in danger of contacting this disease. We present a case of a 42 year old man found dead under a pedestrian bridge with no medical history available. Post mortem computed tomography showed multiple cavities involving upper lobes of both lungs and areas of consolidation in both lung fields raising the suspicion of pulmonary tuberculosis. This was followed by a computed tomography guided lung biopsy and a limited conventional autopsy done in situ in a special high risk autopsy suite with appropriate ventilation. This case highlights the importance of cross sectional imaging which can be coupled with image guided biopsy in cases of infectious disease to reduce the risk of transmission to health care workers.

Post mortem computed tomography (PMCT) guided lung biopsy: A preliminary case report

@#Tuberculosis (TB) is a highly infectious disease on the rise caused by the organism Mycobacterium tuberculosis and health care workers working in emergency departments, medical wards and autopsy rooms are in danger of contacting this disease. We present a case of a 42 year old man found dead under a pedestrian bridge with no medical history available. Post mortem computed tomography showed multiple cavities involving upper lobes of both lungs and areas of consolidation in both lung fields raising the suspicion of pulmonary tuberculosis. This was followed by a computed tomography guided lung biopsy and a limited conventional autopsy done in situ in a special high risk autopsy suite with appropriate ventilation. This case highlights the importance of cross sectional imaging which can be coupled with image guided biopsy in cases of infectious disease to reduce the risk of transmission to health care workers.

Comparison of unbiased stereological estimation of total number of cresyl violet stained neurons and parvalbumin positive neurons in the adult human spiral ganglion.

Estimation of total number of neurons in the spiral ganglion (SG) at various ages and their functional status is important as these neurons are constantly exposed to noise and other environmental factors that may lead to neuronal loss with aging due to excitotoxic damage. Parvalbumin (PV) is a calcium-binding protein (CBP), found in highly metabolically active neurons. It helps in buffering cytosolic calcium, which is essential for neurotransmitter release. The neurons in the adult human SG express PV more strongly than other CBPs like calbindin and calretinin. These CBPs can be used as signatures to recognise neurons. In the present study, we quantified the number of neurons expressing PV by unbiased stereology and compared it to the number of neurons stained by cresyl violet (CV), which is a Nissl stain, in the adult human SG. Five adult human cadaveric temporal bones were obtained from the forensic science mortuary, after due clearance from the institute ethics committee. Independent CV stained and PV immunostained sections were used to estimate the total number of neurons (optical fractionator), with StereoInvestigator (SI) software. The estimated total number of SG neurons was 27,485±3251 and 26,705±1823 in the PV and CV stained sections, respectively. There was no significant difference between the estimates (p=0.552). Therefore, CV staining is simpler and more cost effective when estimating neuronal number. Although PV stains spiral ganglion neurons (SGNs) with a greater intensity and provides a functional status, its tedious protocol limits its use for quantification.

Nuclear morphometry and texture analysis on cytological smears of thyroid neoplasms: a study of 50 cases.

BACKGROUND: Fine needle aspiration cytology (FNAC) is a reliable and reproducible diagnostic technique for thyroid lesions with certain limitations. Computed morphometric methods have been introduced with a view to improve the diagnostic yield of thyroid aspirates. However, a review of the existing literature revealed conflicting reports regarding morphometric parameters in thyroid neoplasms. MATERIALS AND METHODS: This study included 50 cases of thyroid lesions (20 cases of colloid goitre, 15 of follicular adenoma, 5 of follicular carcinoma and 10 papillary carcinomas). Digital images of cytologic smears of these cases were captured using a dedicated photomicrography system and nuclear profiles traced manually. With self-designed image analysis software, nuclear morphometric measurements, including texture analysis, were performed. Discriminant analysis was performed including the morphometric parameters and percentage of correctly classified nuclei noted. RESULTS: Nuclear morphometry parameters showed that papillary thyroid carcinoma had the highest perimeter, area, radius and elongation factor compared to other thyroid lesions. Discriminant analysis revealed that altogether 77.9% of cells could be correctly classified to their lesion category based on the nuclear morphometric and textural parameters. Of the neoplastic cases, 84.5% of cells of follicular neoplasms and 72.5% of papillary carcinoma were classified to the respective category. CONCLUSION: Nuclear morphometry, including texture analysis, can assist in the cytologic diagnosis of thyroid lesions, considering the high degree of accuracy of classification. Further studies and methodological refinements can achieve higher accuracy.

Congenital diverticular disease of the entire colon.

Congenital or true colonic diverticulosis is a rare condition typified by the preservation of the colonic wall architecture within the diverticular outpouching. Cases of multiple jejunal diverticula have been reported as well as cases of solitary giant diverticula of the colon. There have been no reports in the literature of pancolonic congenital diverticulosis.

Hypoxia-induced retinal ganglion cell damage through activation of AMPA receptors and the neuroprotective effects of DNQX.

Hypoxia-induced glutamate accumulation in neural tissues results in damage to neurons through excitotoxic mechanisms via activation of glutamate receptors (GluRs). Here we examine whether hypoxia in the developing retina would cause activation of the ionotropic α-amino-3-hydroxy-5-methylisoxazole-4-propioate (AMPA) GluRs and increase in Ca(2+) influx into retinal ganglion cells (RGCs) that might ultimately lead to their death. Neonatal Wistar rats were subjected to hypoxia for 2h and then sacrificed at various time points after the exposure together with normal age matched control rats. Primary cultures of RGCs were also prepared and subjected to hypoxia. Expression of AMPA glutamate receptor (GluR) 1-4 was examined in the retina. Additionally, expression of GluRs, intracellular Ca(2+) influx, reactive oxygen species (ROS) generation and cell death were investigated in cultured RGCs. GluR1-4 mRNA and protein expression showed a significant increase (P < 0.01) over control values after the hypoxic exposure both in vivo and in vitro. Cells expressing GluR1-4 in the retina were identified as RGCs by double immunofluorescence labeling with Thy1.1. Increased intracellular Ca(2+) in cultured RGCs following hypoxic exposure was reduced (P < 0.01) by 10 µM AMPA antagonist 6, 7-dinitroquinoxaline-2,3-dione (DNQX). Our results suggest that following a hypoxic insult, an increased amount of glutamate accumulates in the neonatal retina. This would then activate AMPA receptors which may damage RGCs through increased Ca(2+) accumulation and ROS generation. The involvement of AMPA receptors in damaging the RGCs is evidenced by suppression of intracellular Ca(2+) influx by DNQX which also decreased ROS generation and cell death by 50%.

Morphometric evaluation of megakaryocytes in bone marrow aspirates of immune-mediated thrombocytopenic purpura.

Immune-mediated thrombocytopenic purpura (ITP), one of the common causes of thrombocytopenia, is characterized by morphologic alterations in megakaryocytes in the bone marrow. Few studies have explored morphometric measurements of megakaryocytes in bone marrow trephine biopsies. Quantitative morphometric analysis of megakaryocytes in bone marrow aspirate smears is lacking in the available literature. This study was aimed at evaluating the morphometric alterations in megakaryocytes in cases of ITP on bone marrow aspirate smears vis-á-vis non-ITP cases. In this study, 35 cases of ITP and 15 non-ITP aspirates were included. The bone marrow aspirate smears were reviewed for diagnosis. Computer-aided image analysis was performed in all aspirate smears for megakaryocytic morphometric measurements, including cytoplasmic and nuclear features. Appropriate statistical tests were applied for comparison. Megakaryocytes in cases of ITP showed a higher nuclear/cytoplasmic ratio (p = 0.021), lower nuclear roundness factor (p = 0.04) and lower nuclear contour ratio (p = 0.027). Cellular circularity and compactness were significantly different in ITP as compared to non-ITP cases, indicating that the megakaryocytes were less round in ITP subjects. Discriminant analysis and cross-validation studies found that 65.5% of megakaryocytes could be correctly classified as ITP or non-ITP. This study shows that significant alterations occur in megakaryocytes in cases of ITP. These changes can potentially be utilized in the development of algorithms for computer-assisted diagnosis of such cases on bone marrow aspirates.

Nuclear factor-kappa ß regulates Notch signaling in production of proinflammatory cytokines and nitric oxide in murine BV-2 microglial cells.

Microglial cells exhibit Notch-1 signaling expression which is enhanced upon activation. We reported previously that enhanced Notch-1 expression in activated microglia modulates production of proinflammatory cytokines and nitric oxide (NO). Furthermore, Notch-1 modulates transcription factor nuclear factor-kappa B (NF-κB). This study was aimed to investigate if NF-κB reciprocally modulates Notch signaling in BV-2 cells. In this connection, the cells were pretreated with caffeic acid phenethyl ester (Cape) followed by stimulating the cells with lipopolysaccharide (LPS). Cape+LPS treatment resulted in reduced translocation of NF-κB into the nucleus. Concomitantly, NF-κB DNA binding activity and the mRNA and protein expression levels of NF-κB/p65, Notch-1, intracellular domain of Notch-1 receptor (NICD), Hes-1, tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß) and inducible nitric oxide synthase (iNOS) along with nitrite level were significantly reduced. Additionally, flow cytometry analysis showed a decrease in expression levels of NF-κB/p65, Notch-1, NICD but an increase in that of signal transducers and activators of transcription 3 (Stat3). Furthermore, nuclear Hes-1, phosphorylated Stat3 (p-Stat3) and recombination signal-binding protein 1 for J-Kappa (RBP-JK) expression levels were significantly suppressed. The present results suggest that Cape inhibits NF-κB activation through suppressing its interaction with DNA. Cape-induced reduction of Hes-1 may be attributed to decreased interaction between NICD and RBP-JK whose levels were reduced concurrently. Hes-1 reduction may lead to decreased production of inflammatory cytokines and NO. It is concluded that NF-κB can modulate Notch-1 signaling. Both pathways operate synergistically for production of proinflammatory cytokines and NO in activated microglia.

Nuclear factor-κB/p65 responds to changes in the Notch signaling pathway in murine BV-2 cells and in amoeboid microglia in postnatal rats treated with the γ-secretase complex blocker DAPT.

Microglial cells constitutively express Notch-1 and nuclear factor-kappaB/p65 (NF-kappaB/p65), and both pathways modulate production of inflammatory mediators. This study sought to determine whether a functional relationship exists between them and, if so, to investigate whether they synergistically regulate common microglial cell functions. By immunofluorescence labeling, real-time polymerase chain reaction (RT-PCR), flow cytometry, and Western blot, BV-2 cells exhibited Notch-1 and NF-kappaB/p65 expression, which was significantly up-regulated in cells challenged with lipopolysaccharide (LPS). This was coupled with an increase in expression of Hes-1, tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta (IL-1beta). In BV-2 cells pretreated with N-[N-(3,5-difluorophenacetyl)-1-alany1]-S-phenyglycine t-butyl ester (DAPT), a gamma-secretase inhibitor, followed by LPS stimulation, Notch-1 expression level was enhanced but that of all other markers was suppressed. Additionally, Hes-1 expression and NF-kappaB nuclear translocation decreased as shown by flow cytometry. Notch-1's modulation of NF-kappaB/p65 was also evidenced in amoeboid microglial cells (AMC) in vivo. In 5-day-old rats given intraperitoneal injections of LPS, Notch-1, NF-kappaB/p65, TNF-alpha, and IL-1beta immunofluorescence in AMC was markedly enhanced. However, in rats given an intraperitoneal injection of DAPT prior to LPS, Notch-1 labeling was augmented, but that of TNF-alpha and IL-1beta was reduced. The results suggest that blocking of Notch-1 activation with DAPT would reduce the level of its downstream end product Hes-1 along with suppression of NF-kappaB/p65 translocation, resulting in suppressed production of proinflammatory cytokines. It is concluded that Notch-1 signaling can trans-activate NF-kappaB/p65 by amplifying NF-kappaB/p65-dependent proinflammatory functions in activated microglia.

Endothelins-1/3 and endothelin-A/B receptors expressing glial cells with special reference to activated microglia in experimentally induced cerebral ischemia in the adult rats.

We reported previously that amoeboid microglial cells (AMC) in the developing brain exhibited endothelins (ETs) expression which diminished with advancing age and was undetected in microglia in the more mature brain. This study sought to explore if microglia in the adult would be induced to express ETs in altered conditions. By immunofluorescence microscopy, ETs and endothelin (ET)-B receptor were undetected in microglial cells in sham-operated and normal control rats. However, in adult rats subjected to middle cerebral artery occlusion (MCAO), lectin labeled activated microglia which occurred in large numbers in the marginal zones in the ischemic cortex at 3 days and 1 week intensely expressed ETs specifically endothelin (ET)-1 and ET-B receptor; ET-3 and ET-A receptor were absent in these cells. By RT-PCR and ELISA, ET-1 and -3 mRNA and protein expression level was progressively increased in the ischemic cerebral cortex after MCAO compared with the controls. ET-A and ET-B receptor mRNA and protein levels were concomitantly up-regulated. It is suggested that increased release of ET-1 following MCAO by massive activated microglia can exert an immediate constriction of local blood vessels bearing ET-A receptor. ET-1 may also interact with activated microglia endowed with ET-B receptor via an autocrine manner that may be linked to chemokines/cytokines production. ET-1, ET-3 and ET-B receptor were also localized in reactive astrocytes along with some oligodendrocytes. We conclude that activated microglia together with other glial cells in the marginal zone after MCAO are the main cellular source of ETs that may be involved in regulation of vascular constriction and glial chemokines/cytokines production. However, dissecting the role of individual component of the endothelin system in the various glial cells, notably activated microglia, would be vital in designing of an effective therapeutic strategy for clinical treatment of stroke in which microglial cells have been implicated.

Melatonin protects periventricular white matter from damage due to hypoxia.

This study investigated the potential of melatonin in ameliorating hypoxic damage to the periventricular white matter (PWM) in the neonatal brain. Vascular endothelial growth factor (VEGF), nitric oxide (NO), glutathione (GSH) and malondialdehyde (MDA) content in the PWM of 1-day-old rats subjected to hypoxia for a period of 2 hr was examined. Vascular endothelial growth factor, NO and MDA concentration was increased whereas that of GSH was reduced after the hypoxic exposure. Additionally, degenerating axons, apoptotic and necrotic cells and vacuolation of capillary endothelial cells were observed in the PWM. The neighboring ependymal and choroid plexus cells also appeared to undergo structural alterations. Increased vascular permeability in the PWM of hypoxic rats was evidenced by the leakage of rhodamine isothiocyanate (RhIC) which was taken up by the amoeboid microglial cells. In vitro experiments showed increased apoptosis in OLN-93 cells, an oligodendrocytic cell line, following hypoxic exposure. Hypoxic rats treated with melatonin showed reduced VEGF, NO and MDA concentrations, increased GSH content and reduced RhIC leakage in the PWM. The ultrastructure of axons, endothelial, ependymal and choroid plexus epithelial cells appeared relatively normal in the hypoxic animals treated with melatonin. The incidence of apoptotic OLN-93 cells was also reduced with melatonin treatment. We suggest that the protective effects of melatonin on various parameters in the PWM of hypoxic neonatal brains were due to its antioxidant properties.

A role for photoreceptors in retinal oedema and angiogenesis: an additional explanation for laser treatment?

PURPOSE: To investigate the possible roles of retinal photoreceptors in macular oedema and retinal angiogenesis with particular reference to the mode of action of laser therapy. METHODS: (i) Studies in rats made hypoxic for 2 h by administering an oxygen/nitrogen mixture of reduced oxygen content, and growth factors determined by RT-PCR, western blotting, and immunohistochemistry. Assessment of blood-retinal barrier integrity using fluorescent and electron-dense tracers. (ii) Studies in pigs with one retina made hypoxic by selective embolisation of the retinal capillary circulation with fluorescent microspheres. (iii) Assessment of laser therapy in selected cases of retinal neovascularisation indicating a role for photoreceptors. RESULTS: In the hypoxic retina, angiogenic and vascular permeability factors such as vascular endothelial growth factor (VEGF), nitric oxide synthases (NOSs), and insulin-like growth factor-1 are upregulated in retinal astrocytes and Müller cells but are also present in large amount in the photoreceptors. Hypoxia-inducible factor-1 (HIF-1) is upregulated in retinal glial cells but not in the photoreceptors, suggesting that growth factors in the photoreceptors may not have been generated there. The tracer dye, rhodium isothiocyanate, leaking from an abnormally permeable inner blood-retinal barrier in the hypoxic retina accumulates in the photoreceptors. CONCLUSIONS: The results indicate that laser treatment of macular oedema or retinal neovascularisation may obtain its effect not only by improving oxygen availability in the inner retina, but also by reducing the load of angiogenic/permeability factors that accumulate in the photoreceptors in hypoxic/ischaemic conditions.

Phytoconstituents as photoprotective novel cosmetic formulations.

Phytoconstituents are gaining popularity as ingredients in cosmetic formulations as they can protect the skin against exogenous and endogenous harmful agents and can help remedy many skin conditions. Exposure of skin to sunlight and other atmospheric conditions causes the production of reactive oxygen species, which can react with DNA, proteins, and fatty acids, causing oxidative damage and impairment of antioxidant system. Such injuries damage regulation pathways of skin and lead to photoaging and skin cancer development. The effects of aging include wrinkles, roughness, appearance of fine lines, lack of elasticity, and de- or hyperpigmentation marks. Herbal extracts act on these areas and produce healing, softening, rejuvenating, and sunscreen effects. We have selected a few photoprotective phytoconstituents, such as curcumin, resveratrol, tea polyphenols, silymarin, quercetin and ascorbic acid, and have discussed the considerations to be undertaken for the development of herbal cosmetic formulations that could reduce the occurrence of skin cancer and delay the process of photoaging. This article is aimed at providing specific and compiled knowledge for the successful preparation of photoprotective herbal cosmetic formulations.

Expression of cyclooxygenase-1/-2, microsomal prostaglandin-E synthase-1 and E-prostanoid receptor 2 and regulation of inflammatory mediators by PGE(2) in the amoeboid microglia in hypoxic postnatal rats and murine BV-2 cells.

This study aimed to investigate the effect of hypoxia on the expression of cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), microsomal prostaglandin-E synthase (mPGES-1), E-prostanoid receptor 2 (EP2) in microglia; and the roles of EP2-cyclic adenosine monophosphate (cAMP) signaling pathway in the prostaglandin E(2) (PGE(2)) regulation of inflammatory mediators released by hypoxic BV-2 cells. Immunoexpression of COX-1, COX-2, mPGES-1 and EP2 was localized in the amoeboid microglial cells (AMC), a nascent brain macrophage in the developing brain, as confirmed by double labeling with OX-42 and lectin, specific markers of microglia. AMC emitted a more intense immunofluorescence in hypoxic rats when compared with the matching controls. In postnatal rats subjected to hypoxia, mRNA and protein expression levels of COX-1, COX-2 and mPGES-1 along with tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), inducible nitric-oxide synthase (iNOS) and PGE(2) product in the callosal tissue were significantly increased. The results were shared in the BV-2 cells except for COX-1 mRNA and protein whose levels remained unaltered. Interestingly, treatment with EP2 antagonist AH-6809 resulted in suppression of hypoxia induced EP2, IL-1beta and iNOS mRNA and protein expression, TNF-alpha protein expression and intracellular cAMP level in BV-2 cells. It is suggested that PGE(2) may regulate above inflammatory mediators in the activated microglia via EP2-cAMP signaling pathway in hypoxic conditions.

Periventricular white matter damage in the hypoxic neonatal brain: role of microglial cells.

Periventricular white matter damage (PWMD) also known as periventricular white matter injury, is one of the major causes of neurological impairment in premature newborns. The etiology of white matter injury is multifaceted with hypoxia-ischemia being an important underlying factor. The developing oligodendrocytes are susceptible to damage resulting in myelination deficits. Excess release of glutamate, free radical production, release of cytokines and iron accumulation are factors thought to mediate damage to the developing white matter. Recent studies have also suggested a role for vascular endothelial growth factor and nitric oxide in the pathogenesis of PWMD. Although the role of microglial cells in the development of PWMD is still debatable, our recent investigations have shed some light on their involvement in the pathogenesis of PWMD. Challenges for the future include in-depth investigation of crosstalk between microglia and immature oligodendrocytes as well as other glial cells and vascular endothelial cells.

Combustion smoke exposure induces up-regulated expression of vascular endothelial growth factor, aquaporin 4, nitric oxide synthases and vascular permeability in the retina of adult rats.

Retinal cells respond to various experimental stimuli including hypoxia, yet it remains to be investigated whether they react to smoke inhalation. We show here that retinal cells in rats, notably the ganglion cells, Müller cells, astrocytes and blood vessels responded vigorously to a smoke challenge. The major changes included up-regulated expression of vascular endothelial growth factor (VEGF), aquaporin 4 (AQP4) and nitric oxide synthase (NOS). VEGF expression was localized in the ganglion cells, Müller cells, astrocytes and associated blood vessels. AQP4 was markedly enhanced in both astrocytes and Müller cells. Increase in vascular permeability after smoke exposure was evidenced by extravasation of serum derived rhodamine isothiocyanate which was internalized by Müller cells and ganglion cells. The tracer leakage was attenuated by aminoguanidine and N(G)-nitro-L-arginine methyl ester (L-NAME) treatment which suppressed retinal tissue NOS and nitric oxide (NO) levels concomitantly. It is suggested that VEGF, AQP4 and NO are involved in increased vascular permeability following acute smoke exposure in which hypoxia was ultimately implicated as shown by blood gases analysis. NOS inhibitors effectively reduced the vascular leakage and hence may ameliorate possible retinal edema in smoke inhalation.

Expression of angiotensin II and its receptors in the normal and hypoxic amoeboid microglial cells and murine BV-2 cells.

Involvement of the local angiotensin receptor system in the central nervous system is well documented, yet its cellular localization and role in the glial cells have remained elusive. This study reports expression of angiotensin II and its receptors namely, angiotensin II receptor type 1 (AT(1)) and angiotensin II receptor type 2 (AT(2)) in the amoeboid microglial cells in the neonatal rat brain. In rats subjected to hypoxia, the amount of angiotensin II released in the corpus callosal tissue was reduced as revealed by enzyme immunoassay. Expression of AT(1) mRNA and protein was down-regulated after hypoxic exposure, but AT(2) was up-regulated. In BV-2 cells exposed to hypoxia for 4 h, expression of AT(1) mRNA was reduced but AT(2) was increased. These changes were further intensified respectively in LPS-stimulated microglia. Edaravone enhanced AT(1) expression but suppressed AT(2) expression significantly in lipopolysaccharide-stimulated cells. Neutralization of AT(2) with its antiserum significantly increased mRNA expression of tumor necrosis factor-alpha and interleukin-1beta but decreased that of transforming growth factor-beta1. In conclusion, the present results suggest that AT(1) may be linked to regulation of vasodilation for increase of blood flow in hypoxic conditions, while up-regulated expression of AT(2) may reduce inflammatory responses through suppression of proinflammatory cytokines and elimination of free radicals.

Kv1.1 expression in microglia regulates production and release of proinflammatory cytokines, endothelins and nitric oxide.

Potassium channels play an important role in microglial activation but their involvement in main functions of microglia including secretion of proinflammatory cytokines has remained uncertain. This study has revealed the specific expression of Kv1.1 in microglia both in vivo and in vitro. Kv1.1 immunoreactivity was localized in the amoeboid microglia in the rat brain between postnatal (P) day 1 (P1) and day 10 (P10); it was, however, progressively reduced with age and was hardly detected at P14 and P21 in ramified microglia, a derivative cell of amoeboid microglia. Following hypoxic exposure, Kv1.1 expression in amoeboid microglia was enhanced or induced in ramified microglia in more mature brain at P21 when compared with their matching controls. RT-PCR and Western blot analysis confirmed Kv1.1 mRNA and protein expression in murine BV-2 cells which was up-regulated by hypoxia or lipopolysaccharide (LPS) treatment; it was reduced significantly by dexamethasone. Neutralization with Kv1.1 antibody suppressed the expression and release of tumor necrosis factor-alpha, interleukin-1beta, endothelins and nitric oxide (NO) in LPS-activated BV-2 cells. It is concluded that Kv1.1, constitutively expressed by microglia, is elicited by hypoxia and LPS and this may be linked to production of proinflammatory cytokines, endothelins and NO.