Assessing the spatial distribution of elemental concentrations in surface sediments of Lake Victoria, Kenya: implications for ecological health and management.

Lacustrine sediment quality indicates the effects of both natural and anthropogenic activities on the ecosystem and communities. Despite its ecological importance, myriad complexities, and potential contaminant sources, the spatial distribution of surficial sediments in Lake Victoria's Winam Gulf has never been comprehensively documented. The purpose of this study was to assess the spatial distribution, pathways, and ecological risk of metal elements in the lake using a sediment matrix. Sediment samples were collected throughout the gulf in November 2022. The concentrations of Al, As, Cd, Co, Cr, Cu, Fe, K, Mn, Mo, Ni, P, Pb, Sb, Sn, Ti, Tl, U, and Zn were compared to different contamination metrics and ecological risk assessment indices. The average concentrations were in the following decreasing order: Zn > > > Cr > > Cu > Ni > Pb > Co > As > Cd with mean (± SD) of 185 ± 45 mg kg-1, 56 ± 15 mg kg-1, 45 ± 16 mg kg-1, 37 ± 11 mg kg-1, 24 ± 5 mg kg-1, 20 ± 7 mg kg-1, 3.9 ± 1.3 mg kg-1, 0.30 ± 0.09 mg kg-1, respectively, with strong indications of anthropogenic sources. Average concentrations were in the following decreasing order: Zn > > > Cr, Cu, Ni, Pb, Co, As, and Cd levels (mean ± SD) were 185 ± 45 mg kg-1, 56 ± 15 mg kg-1, 45 ± 16 mg kg-1, 37 ± 11 mg kg-1, 24 ± 5 mg kg-1, 20 ± 7 mg kg-1, 3.9 ± 1.3 mg kg-1 and 0.30 ± 0.09 mg kg-1 with strong indications of anthropogenic sources. The geo-accumulation index (Igeo) and enrichment factor categorisation schemes, respectively, classified these as uncontaminated (level 0) and depletion to minimal enrichment (level 1), while the ecological risk analysis classified them as "low risk". The mouth of the Nyando River, as well as Kisumu, Kendu, and Homa bays, were the most element-enriched and should be prioritised for focused monitoring and remediation. As a result, targeted land management of urban, industrial, transportation, and agricultural areas offers the opportunity to reduce sediment inputs into the lake ecosystem.

Considerations for environmental biogeochemistry and food security for aquaculture around Lake Victoria, Kenya.

The impact of population expansion through economic growth and development has been identified as one of the key drivers of both water and sediment contamination from potentially harmful elements (PHEs). This presents a major hazard not only to aquatic ecosystems but local riparian communities and beyond who rely heavily on this natural resource for drinking water and fish-a valuable source of dietary micronutrients and protein. The present study measured biogeochemical concentration of PHEs in water, sediment and fish from locations pooled into four zones within Winam Gulf and Lake Victoria area of Kenya. Captured fish were used as a sentinel receptor of lake health to evaluate potential risks to fisheries and aquaculture food security. In water, concentrations of arsenic (As), cadmium (Cd), chromium (Cr), copper (Cu) and lead (Pb) were observed above the United States Environmental Protection Agency (US EPA) maximum contamination level drinking water guidelines (MCL), with aluminium (Al) observed above the Aquatic Life Criteria in all four zones. Similarly, sediment concentrations in all four zones exceeded the US EPA Effects range low (ERL) threshold guidelines for Cu, nickel (Ni), zinc (Zn) and Pb, with Cu, Zn and Pb classed at moderate contamination levels using the contamination factor. Fish tissue concentrations from the four zones were calculated using recommended daily intakes (RDI) and for PHEs as provisional maximum tolerable intakes (PMTIs) and indicated most macro- and micronutrients were at or below 10% RDI from aquaculture and wild fish, with Se indicating a greater RDI (16-29%) in all the zones. Contributions of PHEs to PMTIs were below threshold guidelines for both aquaculture and wild fish with only Cd, Cr and Pb levels being above the PMTI thresholds. There is a need to assess the long-term effects of persistent anthropogenic PHE input into Winam Gulf and the wider Lake Victoria basin. Continued monitoring of PHEs using both historical and more recent data will enable future management policies to be implemented through improved mitigation strategies to reduce their impact on water quality, fish health and subsequent human health.

Developments in Pb-210 methodologies to provide chronologies for environmental change.

Chronologies generated from core profiles to apply dates to environmental changes commonly use the measurement of the activity of radionuclides deposited and stratified with physical environmental material. The most commonly reported nuclide to define chronologies covering the last 150 years is Pb-210, for which accepted data processing methodologies in the literature have focussed on the constant rate of supply (CRS) model and the more recently published Bayesian Plum model. This short communication describes a validation approach using defined sediment layers referred to as 'varve' counting, which provide known points of reference to account for uncertainty between generated dates from each model using published Pb-210 measurements. A significant improvement in the chronologies was observed when applying reference date corrections to the models. This was shown to be essential in providing confidence in reported datasets and accuracy of predicted chronologies, which will better inform the interpretation of environmental change, e.g. sedimentation rates, climate change, pollution pathways and land degradation. Generated chronologies from both the CRS and Plum methods showed good agreement with the established varve dates (typically < 4-year difference).

The willingness of UK adults with intellectual disabilities to take COVID-19 vaccines.

BACKGROUND: Given the much greater COVID-19 mortality risk experienced by people with intellectual disabilities (ID), understanding the willingness of people with ID to take a COVID-19 vaccine is a major public health issue. METHOD: In December 2020 to February 2021, across the United Kingdom, 621 adults with ID were interviewed remotely and 348 family carers or support workers of adults with ID with greater needs completed an online survey, including a question on willingness to take a COVID-19 vaccine if offered. RESULTS: Eighty-seven per cent of interviewees with ID were willing to take a COVID-19 vaccine, with willingness associated with white ethnicity, having already had a flu vaccine, gaining information about COVID-19 from television but not from social media, and knowing COVID-19 social restrictions rules. A percentage of 81.7% of surveyed carers of adults with ID with greater needs reported that the person would be willing to take a COVID-19 vaccine, with willingness associated with white ethnicity, having a health condition of concern in the context of COVID-19, having had a flu vaccine, being close to someone who had died due to COVID-19, and having shielded at some point during the pandemic. CONCLUSIONS: Reported willingness to take the COVID-19 vaccine is high among adults with ID in the United Kingdom, with factors associated with willingness having clear implications for public health policy and practice.

Elemental composition of aquaculture fish from West Bengal, India: nutrition versus food safety.

Aquaculture production continues to grow in West Bengal, where on average people consume 8.2 kg capita-1 of fish each year, and an extensive mosaic of aquaculture ponds has developed along the River Hugli as clay pits are repurposed. The adjacent brickworks and industry (especially tanneries) are a source of environmental pollution, with potential for bioaccumulation of potentially harmful elements (PHEs) in fish farmed in these ponds. Fish from aquaculture present an opportunity to meet food sufficiency in West Bengal; however, an investigation to assess their effectiveness for micronutrient supply balanced against food safety is required. Five ponds close to industrial brick manufacture (urban) and three from rural areas were assessed for the degree of pollution within their pond sediments and waters. Fish were also sampled from each location including a subset from the market in Kolkata to determine the concentrations of PHEs in their fish muscle tissue. Dietary intake and PHE loading were calculated for four fish species to evaluate their nutrient content with respect to recommended daily intakes for adults, e.g. calcium (Ca), potassium (K), magnesium (Mg), iron (Fe), zinc (Zn) and selenium (Se), and to establish whether the provisional maximum tolerable intakes (PMTIs) are exceeded for PHEs, e.g. aluminium (Al), arsenic (As), mercury (Hg), chromium (Cr), tin (Sn), copper (Cu) and lead (Pb). Preliminary results suggest that aquaculture is making an important contribution to nutrition, with fish being a good source of Se. However, in contrast to small wild-caught fish, aquaculture fish in the present study were poor sources of Fe, Ca and Zn. The fish also made substantial contributions (> 10%) to the PMTI of Hg and As. Therefore, there is an urgent need for ongoing monitoring and an expanded sampling programme, as well as research into approaches which might improve the nutritional quality of the farmed fish.

Acquired immune responses to the seasonal trivalent influenza vaccination in COPD.

Epidemiological data suggest that influenza vaccination protects against all-cause mortality in chronic obstructive pulmonary disease (COPD) patients. However, recent work has suggested there is a defect in the ability of some COPD patients to mount an adequate humoral response to influenza vaccination. The aim of our study was to investigate humoral and cell-mediated vaccine responses to the seasonal trivalent influenza vaccination (TIV) in COPD subjects and healthy controls. Forty-seven subjects were enrolled into the study; 23 COPD patients, 13 age-matched healthy controls (HC ≥ 50) and 11 young healthy control subjects (YC ≤ 40). Serum and peripheral blood mononuclear cells (PBMC) were isolated pre-TIV vaccination and at days 7 and 28 and 6 months post-vaccine for haemagglutinin inhibition (HAI) titre, antigen-specific T cell and antibody-secreting cell analysis. The kinetics of the vaccine response were similar between YC, HC and COPD patients and there was no significant difference in antibody titres between these groups at 28 days post-vaccine. As we observed no disease-dependent differences in either humoral or cellular responses, we investigated if there was any association of these measures with age. H1N1 (r = -0·4253, P = 0·0036) and influenza B (r = -0·344, P = 0·0192) antibody titre at 28 days negatively correlated with age, as did H1N1-specific CD4+ T helper cells (r = -0·4276, P = 0·0034). These results suggest that age is the primary determinant of response to trivalent vaccine and that COPD is not a driver of deficient responses per se. These data support the continued use of the yearly trivalent vaccine as an adjunct to COPD disease management.

Comparison of a novel microcrystalline tyrosine adjuvant with aluminium hydroxide for enhancing vaccination against seasonal influenza.

BACKGROUND: Vaccination against seasonal influenza strains is recommended for "high risk" patient groups such as infants, elderly and those with respiratory or circulatory diseases. However, efficacy of the trivalent influenza vaccine (TIV) is poor in many cases and in the event of an influenza pandemic, mono-valent vaccines have been rapidly developed and deployed. One of the main issues with use of vaccine in pandemic situations is the lack of a suitable quantity of vaccine early enough during the pandemic to exert a major influence on the transmission of virus and disease outcome. One approach is to use a dose-sparing regimen which inevitably involves enhancing the efficacy using adjuvants. METHODS: In this study we compare the use of a novel microcrystalline tyrosine (MCT) adjuvant, which is currently used in a niche area of allergy immunotherapy, for its ability to enhance the efficacy of a seasonal TIV preparation. The efficacy of the MCT adjuvant formulation was compared to alum adjuvanted TIV and to TIV administered without adjuvant using a ferret challenge model to determine vaccine efficacy. RESULTS: The MCT was found to possess high protein-binding capacity. In the two groups where TIV was formulated with adjuvant, the immune response was found to be higher (as determined by HAI titre) than vaccine administered without adjuvant and especially so after challenge with a live influenza virus. Vaccinated animals exhibited lower viral loads (as determined using RT-PCR) than control animals where no vaccine was administered. CONCLUSIONS: The attributes of each adjuvant in stimulating single-dose protection against a poorly immunogenic vaccine was demonstrated. The properties of MCT that lead to the reported effectiveness warrants further exploration in this and other vaccine targets - particularly where appropriate immunogenic, biodegradable and stable alternative adjuvants are sought.

Dirofilariasis mouse models for heartworm preclinical research.

Introduction: Dirofilariasis, including heartworm disease, is a major emergent veterinary parasitic infection and a human zoonosis. Currently, experimental infections of cats and dogs are used in veterinary heartworm preclinical drug research. Methods: As a refined alternative in vivo heartworm preventative drug screen, we assessed lymphopenic mouse strains with ablation of the interleukin-2/7 common gamma chain (γc) as susceptible to the larval development phase of Dirofilaria immitis. Results: Non-obese diabetic (NOD) severe combined immunodeficiency (SCID)γc-/- (NSG and NXG) and recombination-activating gene (RAG)2-/-γc-/- mouse strains yielded viable D. immitis larvae at 2-4 weeks post-infection, including the use of different batches of D. immitis infectious larvae, different D. immitis isolates, and at different laboratories. Mice did not display any clinical signs associated with infection for up to 4 weeks. Developing larvae were found in subcutaneous and muscle fascia tissues, which is the natural site of this stage of heartworm in dogs. Compared with in vitro-propagated larvae at day 14, in vivo-derived larvae had completed the L4 molt, were significantly larger, and contained expanded Wolbachia endobacteria titres. We established an ex vivo L4 paralytic screening system whereby assays with moxidectin or levamisole highlighted discrepancies in relative drug sensitivities in comparison with in vitro-reared L4 D. immitis. We demonstrated effective depletion of Wolbachia by 70%-90% in D. immitis L4 following 2- to 7-day oral in vivo exposures of NSG- or NXG-infected mice with doxycycline or the rapid-acting investigational drug, AWZ1066S. We validated NSG and NXG D. immitis mouse models as a filaricide screen by in vivo treatments with single injections of moxidectin, which mediated a 60%-88% reduction in L4 larvae at 14-28 days. Discussion: Future adoption of these mouse models will benefit end-user laboratories conducting research and development of novel heartworm preventatives via increased access, rapid turnaround, and reduced costs and may simultaneously decrease the need for experimental cat or dog use.

Defective interfering viruses and their potential as antiviral agents.

Defective interfering (DI) virus is simply defined as a spontaneously generated virus mutant from which a critical portion of the virus genome has been deleted. At least one essential gene of the virus is deleted, either in its entirety, or sufficiently to make it non-functional. The resulting DI genome is then defective for replication in the absence of the product(s) of the deleted gene(s), and its replication requires the presence of the complete functional virus genome to provide the missing functions. In addition to being defective DI virus suppresses production of the helper virus in co-infected cells, and this process of interference can readily be observed in cultured cells. In some cases, DI virus has been observed to attenuate disease in virus-infected animals. In this article, we review the properties of DI virus, potential mechanisms of interference and progress in using DI virus (in particular that derived from influenza A virus) as a novel type of antiviral agent.

Lysyl-tRNA synthetase produces diadenosine tetraphosphate to curb STING-dependent inflammation.

Inflammation is an essential part of immunity against pathogens and tumors but can promote disease if not tightly regulated. Self and non-self-nucleic acids can trigger inflammation, through recognition by the cyclic GMP-AMP (cGAMP) synthetase (cGAS) and subsequent activation of the stimulator of interferon genes (STING) protein. Here, we show that RNA:DNA hybrids can be detected by cGAS and that the Lysyl-tRNA synthetase (LysRS) inhibits STING activation through two complementary mechanisms. First, LysRS interacts with RNA:DNA hybrids, delaying recognition by cGAS and impeding cGAMP production. Second, RNA:DNA hybrids stimulate LysRS-dependent production of diadenosine tetraphosphate (Ap4A) that in turn attenuates STING-dependent signaling. We propose a model whereby these mechanisms cooperate to buffer STING activation. Consequently, modulation of the LysRS-Ap4A axis in vitro or in vivo interferes with inflammatory responses. Thus, altogether, we establish LysRS and Ap4A as pharmacological targets to control STING signaling and treat inflammatory diseases.

Source, distribution and ecotoxicological assessment of multielements in superficial sediments of a tropical turbid estuarine environment: A multivariate approach.

The work examined the distribution, possible sources and ecotoxicological assessment of 51 trace elements covering 13 sampling stations in surface sediments of coastal regions of Sundarban mangrove wetland and adjacent Hugli river estuary. The element concentrations exhibited an increasing trend towards downstream of the estuary (except lanthanides) with maximum enrichment for 22 elements at Gangadharpur (Sundarban region). According to Sediment Quality Guidelines (SQGs), the concentrations of Cu, As, Cr and Cd exceeded the Effects-Range-Low values, while Ni at certain stations exceeded the Effects-Range-Medium suggesting adverse effects on the sediment-dwelling organisms. The geoaccumulation index revealed that the stations were unpolluted to moderately polluted. Risk Index (357.61) and Enrichment factor (11.42) depicted that Nimtala station (upstream) was at high ecological risk zone. The result of PCA endorsed that organic carbon and clay fraction play crucial role in accumulating the elements in sediments. This pilot study contributes to a better understanding of the geochemistry of this complex deltaic ecosystem.

Telomerase repressor sequences on chromosome 3 and induction of permanent growth arrest in human breast cancer cells.

BACKGROUND: Activation of the enzyme telomerase, which has been associated with cellular immortality, may constitute a key step in the development of human cancer. Telomerase is repressed in most normal human somatic cells. This study was conducted, using a genetic complementation approach, with the aim of identifying and mapping the genes responsible for repressing telomerase and, simultaneously, to establish the effect of experimentally induced telomerase repression on human tumor cell growth. METHODS: Individual human chromosomes isolated from normal diploid cells and tagged with bacterial antibiotic resistance genes (for later selection) were introduced into cells of the human breast carcinoma cell line 21NT by means of microcell transfer. Selected hybrid clones were screened for telomerase activity by use of the polymerase chain reaction-based telomere repeat amplification protocol (TRAP) assay, and the proliferative fate of the hybrid clones was determined. Regions of the introduced chromosomes associated with telomerase repression were mapped using segregant hybrids and a deletion analysis that employed microsatellite DNA markers. RESULTS: Strong repression of telomerase was observed following transfer of human chromosome 3 into 21NT cells but not after transfer of chromosomes 8, 12, or 20. The vast majority of hybrid clones with repressed telomerase entered permanent growth arrest after 10-18 population doublings. Deletion analysis of nonrepressed segregant monochromosome 3 hybrids indicated two regions on the short arm of chromosome 3 (3p21.3-p22 and 3p12-21.1) where telomerase regulator genes may be located. CONCLUSIONS: Telomerase in human breast cancer cells is efficiently repressed by a gene or genes on normal human chromosome 3p, and this repression is associated with permanent growth arrest of the tumor cells.

Performance and learning curve of a surgical care practitioner in completing hip aspirations.

INTRODUCTION The roles of non-medically trained practitioners within the NHS are expanding; they are now being employed by many specialties, including surgery, to relieve pressures on healthcare teams. AIMS To investigate the learning curve and competence of an orthopaedic surgical care practitioner (SCP) in performing hip aspirations. METHODS Data were retrospectively collected on 510 orthopaedic hip aspirations, of which 360 were completed by a single SCP and 150 were completed by surgeons before the SCP took over routine aspiration. The 360 aspirations completed by an SCP were separated into groups of 30 by date, so any trend in failure rate could be analysed. Ordinal χ2 analysis was used to analyse this trend and Pearson χ2 analysis was used to analyse differences in failure rates between professionals. RESULTS The hip aspiration failure rate for the SCP was significantly lower than for the surgeons; 8.6% vs 20.7% (P<0.001). With the experience gained in completing the first 210 procedures, the failure rate of the SCP dropped to 3.3% for the remaining 150 procedures. This downward trend in hip aspiration failure rate, with advancing experience of the SCP, was shown to be statistically significant (P=0.006). DISCUSSION SCPs who complete hip aspirations on a regular basis have significantly lower failure rates than surgeons, probably as a result of the learning curve, which this study demonstrated. Other trusts should consider delegating routine hip aspiration work to a designated SCP to lower failure rates.

RNA probes detect nucleotide sequence homology between members of two different nairovirus serogroups.

Cloned cDNA derived from the small (S) and medium (M) genomic RNA segments of Dugbe (DUG) virus, isolate ArD44313, a member of the Nairobi sheep disease (NSD) serogroup of nairoviruses (family, Bunyaviridae) was used to prepare 32P-labelled DNA and RNA probes. The S and M segments of six isolates of DUG virus all hybridised to both DNA and RNA probes, although the M segment of isolate KT281/75 reacted only weakly. Of nine other nairoviruses tested, representing all the six other serogroups within the Nairovirus genus, none hybridised to the DNA probes. However, under conditions of low stringency, the DUG S and M RNA probes hybridised to the respective S and M segments of Ganjam (GAN) virus (another member of the NSD serogroup). The DUG S RNA probe also hybridised to the S segments of Crimean-Congo haemorrhagic fever (CCHF) virus and Hazara (HAZ) virus (members of the CCHF serogroup). The indicated sequence relationships between DUG, GAN, CCHF and HAZ viruses show that the NSD serogroup is more closely related to members of the CCHF serogroup than it is to nairoviruses of the other five serogroups.

Expression of the nucleocapsid protein of Dugbe virus and antigenic cross-reactions with other nairoviruses.

The small (S) RNA segment of Dugbe (DUG) virus (Nairovirus, Bunyaviridae) encodes a single protein, the nucleocapsid (N) protein, of M(r) 49.4 kDa. cDNA derived from the complete coding region for the N protein was cloned into Autographa californica nuclear polyhedrosis virus (AcNPV) under control of the polyhedrin promoter and used to infect Spodoptera frugiperda insect cells. Western blotting analysis using monoclonal antibodies demonstrated the production of DUG N protein in the infected cells. Monoclonal and polyclonal antibodies to the N protein of Crimean-Congo haemorrhagic fever (CCHF) virus were found to cross-react weakly with the baculovirus expressed DUG N protein by Western blotting. When used in an enzyme linked immunoassay (ELISA), the DUG N protein reacted with polyclonal mouse immune ascitic fluids raised against either CCHF or Hazara viruses (both members of the CCHF serogroup of nairoviruses). Cross-reactions between DUG virus (Nairobi sheep disease serogroup) and members of other nairovirus serogroups were not detected.

Pharmacological evidence for the subclassification of central dopamine receptors in the rat.

1 The relative potencies of dopamine receptor agonists in causing stereotypy in rats when injected into the olfactory tubercles, and contralateral rotation when injected unilaterally into the caudate nucleus of rats with lesions of the nigro-striatal dopamine pathway, were determined. The actions of some agonists in eliciting these responses following peripheral injection, and the relative potencies of dopamine receptor antagonists in inhibiting them were also determined. 2 Dopamine, apomorphine and 2-amino-5,6 and 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (A-5, 6 DTN, A-6, 7 DTN) and N,N dipropyl A-5, 6DTN induced both responses. In contrast, 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine HCl (SK & F 38393) whether injected intracerebrally or peripherally, induced contralateral rotation but not stereotypy. 3 Contralateral rotation and stereotypy induced by apomorphine or N,N dipropyl A-5, 6 DTN were inhibited by haloperidol, pimozide and fluphenazine but these drugs failed to inhibit rotation induced by SK & F 38393. Clozapine inhibited rotation induced by SK & F 38393, apomorphine or N,N dipropyl A-5,6 DTN but failed to inhibit stereotypy. Loxapine was more potent in inhibiting stereotypy than rotation,, whereas clothiapine inhibited rotation and stereotypy at similar doses irrespective of the agonist used to elicit the response. 4 Contralateral rotation induced by SK & F 38393 was not inhibited by yohimbine, prazosin, atropine, methysergide, mepyramine or propranolol. 5 The results provide evidence that contralateral rotation induced by dopamine receptor agonists is mediated by two different classes of dopamine receptors and that these receptors differ from those mediating the stereotypy response. 6 The receptors mediating these responses appear classifiable in terms of their sensitivity to the agonist actions of SK & F 38393 or apomorphine respectively. SK & F 38393-sensitive receptors are susceptible to blockade by clozapine but are not blocked by haloperidol, pimozide or fluphenazine. Apomorphine-sensitive receptors are susceptible to blockade by haloperidol, pimozide and fluphenazine but appear divisible into two sub-classes depending on whether or not they are blocked by clozapine and on their sensitivity to blockade by loxapine.

Failure of SKF 38393-A to relieve parkinsonian symptoms induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the marmoset.

Chronic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced parkinsonian symptoms, predominantly bradykinesia and tremor, in marmosets. These symptoms were reduced by L-DOPA plus benserazide but the putative D1-receptor agonist SKF 38393-A did not affect tremor and increased the bradykinesia. Neither treatment affected behaviour in normal marmosets. It is suggested that D1-receptor agonists are unlikely to be effective in the treatment of Parkinson's disease.

Alpha 2-adrenoceptors mediate clonidine-induced sedation in the rat.

1 The central alpha-adrenoceptors responsible for mediating clonidine-induced sedation in rats have been characterized according to their sensitivity to alpha-adrenoceptor agonists and antagonists.2 Clonidine, injected intraperitoneally or intracerebroventricularly, caused dose-dependent sedation, both in terms of a reduction in the time that rats could remain on an accelerating rotarod and in terms of overt sedation assessed visually. Following intracerebroventricular injection, xylazine, naphazoline and methoxamine, but not phenylephrine, produced similar effects.3 The sedation caused by intraperitoneal injection of clonidine was antagonized by intracerebroventricularly injected phentolamine, yohimbine, piperoxan and tolazoline but not by labetalol, thymoxamine or prazosin.4 The relative potencies of the agonists in causing sedation and of the antagonists in inhibiting the sedative effect of clonidine clearly demonstrated that the central alpha-adrenoceptors mediating clonidine-induced sedation are the same as the peripheral presynaptic alpha(2)-adrenoceptors.5 All the alpha-adrenoceptor agonists caused hypothermia after intracerebroventricular injection, but their order of potency was different from that in producing sedation. The hypothermic effect of intraperitoneally injected clonidine was little affected by any of the antagonists administered intracerebroventricularly. No conclusions could be drawn concerning the type of receptor responsible for mediating hypothermia.