Soluble epoxide hydrolase inhibition reverses cognitive dysfunction in a mouse model of metabolic syndrome by modulating inflammation.

Midlife metabolic syndrome (MetS) is associated with cognitive impairment in late life. The mechanism of delayed MetS-related cognitive dysfunction (MetSCD) is not clear, but it has been linked to systemic inflammation and chronic cerebral microangiopathy. Currently there is no treatment for late life MetSCD other than early risk factor modification. We investigated the effect of soluble epoxide hydrolase (sEH) inhibitor 4-[[trans-4-[[(tricyclo[3.3.1.13,7]dec-1-ylamino)carbonyl]amino]cyclohexyl]oxy]-benzoic acid (t-AUCB) on cognitive performance, cerebral blood flow (CBF), and central and peripheral inflammation in the high-fat diet (HFD) model of MetS in mice. At 6 weeks of age, male mice were randomly assigned to receive either HFD or standard chow (STD) for 6 months. Mice received either t-AUCB or vehicle for 4 weeks. Cognitive performance was evaluated, followed by CBF measurement using magnetic resonance imaging (MRI). At the end of the study, blood was collected for measurement of eicosanoids and inflammatory cytokines. The brains were then analyzed by immunohistochemistry for glial activation markers. The HFD caused a significant impairment in novel object recognition. Treatment with t-AUCB increased plasma levels of 14,15-EET, prevented this cognitive impairment and modified hippocampal glial activation and plasma cytokine levels, without affecting CBF in mice on HFD. In conclusion, sEH inhibition for four weeks prevents cognitive deficits in mice on chronic HFD by modulating inflammatory processes without affecting CBF.

Sex Difference in Capillary Reperfusion After Transient Middle Cerebral Artery Occlusion in Diabetic Mice.

BACKGROUND: Type 2 diabetes (DM2) exacerbates stroke injury, reduces efficacy of endovascular therapy, and worsens long-term functional outcome. Sex differences exist in stroke incidence, response to therapy, poststroke microvascular dysfunction, and functional recovery. In this study, we tested the hypotheses that poor outcome after stroke in the setting of DM2 is linked to impaired microvascular tissue reperfusion and that male and female DM2 mice exhibit different microvascular reperfusion response after transient middle cerebral artery occlusion (MCAO). METHODS: Transient MCAO was induced for 60 minutes using an intraluminal filament in young adult DM2 and nondiabetic control male and female mice. Capillary flux in deep cortical layers was assessed using optical coherence tomography-based optical microangiography (OMAG), and associated regional brain infarct size was evaluated by hematoxylin and eosin staining. RESULTS: Compared to baseline, MCAO reduced absolute capillary red blood cell flux by 84% at 24 hours post-MCAO in male DM2 (P<0.001) but not male control mice. When normalized to pre-MCAO baseline, red blood cell flux 24 hours after stroke was 64% lower in male DM2 mice than male nondiabetic controls (P<0.01). In females, MCAO decreased capillary flux by 48% at 24 hours post-MCAO compared with baseline in DM2 (P<0.05) but not in control mice. Red blood cell flux of female DM2 mice did not differ from that of nondiabetic controls either before or 24 hours after MCAO. Furthermore, normalized capillary flux 24 hours after MCAO failed to differ between female DM2 mice and nondiabetic controls. Concomitantly, male but not female DM2 mice experienced 25% larger infarct in caudate-putamen versus respective nondiabetic controls (P<0.05). CONCLUSIONS: DM2 impairs capillary perfusion and exacerbates ischemic deep brain injury in male but not female young adult mice. Premenopausal females appear to be protected against DM2-related capillary dysfunction and brain injury.

Fluid dynamics in aging-related dementias.

Recent human and animal model experimental studies revealed novel pathways for fluid movement, immune cell trafficking and metabolic waste clearance in CNS. These studies raise the intriguing possibility that the newly discovered pathways, including the glymphatic system, lymphatic meningeal vessels and skull-brain communication channels, are impaired in aging and neurovascular and neurodegenerative diseases associated with dementia, including Alzheimer's disease (AD) and AD-related dementia. We provide an overview of the glymphatic and dural meningeal lymphatic systems, review current methods and approaches used to study glymphatic flow in humans and animals, and discuss current evidence and controversies related to its role in CNS flow homeostasis under physiological and pathophysiological conditions. Non-invasive imaging approaches are needed to fully understand the mechanisms and pathways driving fluid movement in CNS and their roles across lifespan including healthy aging and aging-related dementia.

A CMOS compatible thermoelectric device made of crystalline silicon membranes with nanopores.

Herein, we report the use of nanostructured crystalline silicon as a thermoelectric material and its integration into thermoelectric devices. The proof-of-concept relies on the partial suppression of lattice thermal conduction by introducing pores with dimensions scaling between the electron mean free path and the phonon mean free path. In other words, we artificially aimed at the well-known 'electron crystal and phonon glass' trade-off targeted in thermoelectricity. The devices were fabricated using CMOS-compatible processes and exhibited power generation up to 5.5 mW cm-2under a temperature difference of 280 K. These numbers demonstrate the capability to power autonomous devices with environmental heat sources using silicon chips of centimeter square dimensions. We also report the possibility of using the developed devices for integrated thermoelectric cooling.

Soluble Epoxide Hydrolase Blockade after Stroke Onset Protects Normal but Not Diabetic Mice.

Soluble epoxide hydrolase (sEH) is abundant in the brain, is upregulated in type 2 diabetes mellitus (DM2), and is possible mediator of ischemic injury via the breakdown of neuroprotective epoxyeicosatrienoic acids (EETs). Prophylactic, pre-ischemic sEH blockade with 4-[[trans-4-[[(tricyclo[3.3.1.13,7]dec-1-ylamino)carbonyl]amino]cyclohexyl]oxy]-benzoic acid (tAUCB) reduces stroke-induced infarct in normal and diabetic mice, with larger neuroprotection in DM2. The present study tested whether benefit occurs in normal and DM2 mice if tAUCB is administered after stroke onset. We performed 60 min middle cerebral artery occlusion in young adult male C57BL mice divided into four groups: normal or DM2, with t-AUCB 2 mg/kg or vehicle 30 min before reperfusion. Endpoints were (1) cerebral blood flow (CBF) by laser Doppler, and (2) brain infarct at 24 h. In nondiabetic mice, t-AUCB reduced infarct size by 30% compared to vehicle-treated mice in the cortex (31.4 ± 4 vs. 43.8 ± 3 (SEM)%, respectively) and 26% in the whole hemisphere (26.3 ± 3 vs. 35.2 ± 2%, both p < 0.05). In contrast, in DM2 mice, tAUCB failed to ameliorate either cortical or hemispheric injury. No differences were seen in CBF. We conclude that tAUCB administered after ischemic stroke onset exerts brain protection in nondiabetic but not DM2 mice, that the neuroprotection appears independent of changes in gross CBF, and that DM2-induced hyperglycemia abolishes t-AUCB-mediated neuroprotection after stroke onset.

Nevi, Ambient Ultraviolet Radiation, and Thyroid Cancer Risk: A French Prospective Study.

BACKGROUND: Incidence rates have increased considerably worldwide for both differentiated thyroid cancer and cutaneous melanoma, and two-way associations between these neoplasms have been described. Whether melanoma risk factors are associated with thyroid cancer risk remains unknown. METHODS: Using Cox regression modeling, we prospectively analyzed the relationship between self-reported pigmentary traits, baseline residential ultraviolet (UV) exposure, and thyroid cancer risk in 86,960 women from the E3N cohort, followed-up over 1990-2008 through biennial questionnaires. We assessed associations of pigmentary traits and UV exposure with personal history of benign thyroid diseases using logistic regression modeling. All statistical tests were two sided. RESULTS: In models adjusted for age and thyroid cancer risk factors, number of nevi was positively associated with thyroid cancer risk ("very many" vs. "none": hazards ratio [HR] = 1.7, 95% confidence interval [CI] = 1.0, 2.8; Ptrend = 0.01), independently of residential UV exposure or iodine intake. Risk was inversely associated with latitude and positively associated with mean daily UV level at baseline (HRs for the fourth vs. first quartile of latitude and spring/summer UVB level = 0.7, 95% CI = 0.5, 0.9; Ptrend = 0.03, and HR = 1.9, 95% CI = 1.4, 2.7; Ptrend = 0.02, respectively); associations were restricted to women with dietary iodine below the median intake. Number of nevi and UV level were also associated with personal histories of dysthyroidism and of goiter/nodules, although more weakly so. CONCLUSIONS: Our results suggest that number of nevi and residential UV exposure are associated with the risks of thyroid cancer and benign conditions. They point to novel pathways in thyroid cancer or melanoma etiologies and warrant replication.

A microfluidic platform integrating functional vascularized organoids-on-chip.

The development of vascular networks in microfluidic chips is crucial for the long-term culture of three-dimensional cell aggregates such as spheroids, organoids, tumoroids, or tissue explants. Despite rapid advancement in microvascular network systems and organoid technologies, vascularizing organoids-on-chips remains a challenge in tissue engineering. Most existing microfluidic devices poorly reflect the complexity of in vivo flows and require complex technical set-ups. Considering these constraints, we develop a platform to establish and monitor the formation of endothelial networks around mesenchymal and pancreatic islet spheroids, as well as blood vessel organoids generated from pluripotent stem cells, cultured for up to 30 days on-chip. We show that these networks establish functional connections with the endothelium-rich spheroids and vascular organoids, as they successfully provide intravascular perfusion to these structures. We find that organoid growth, maturation, and function are enhanced when cultured on-chip using our vascularization method. This microphysiological system represents a viable organ-on-chip model to vascularize diverse biological 3D tissues and sets the stage to establish organoid perfusions using advanced microfluidics.

Attenuation of post-myocardial infarction depression in rats by n-3 fatty acids or probiotics starting after the onset of reperfusion.

Proinflammatory cytokines play a central role in depression-like behaviour and apoptosis in the limbic system after myocardial infarction (MI). A PUFA n-3 diet or the combination of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 probiotics, when given before the ischaemic period, reduce circulating proinflammatory cytokines as well as apoptosis in the limbic system. The present study was designed to determine if the same nutritional interventions maintain their beneficial effects when started after the onset of the reperfusion period and attenuate depression-like behaviour observed after MI. MI was induced by the occlusion of the left anterior descending coronary artery for 40 min in rats. After the onset of reperfusion, animals were fed with a high- or low-PUFA n-3 diet, combined or not with one billion live bacteria of L. helveticus and B. longum. At 3 d post-MI, caspase-3 enzymatic activities and terminal 2'-deoxyuridine, 5'-triphosphate (dUTP) nick-end labelling (TUNEL)-positive cells were decreased in the CA1, dentate gyrus (DG) and amygdala with the high-PUFA n-3 diet, as compared to the three other diets. Probiotics attenuated caspase-3 activity and TUNEL-positive cells in the DG and the medial amygdala. At 2 weeks post-MI, depression-like behaviour was observed in the low-PUFA n-3 diet without probiotics-group, and this behaviour was attenuated with the high-PUFA n-3 diet or/and probiotics. These results indicate that a high-PUFA n-3 diet or the administration of probiotics, starting after the onset of reperfusion, are beneficial to attenuate apoptosis in the limbic system and post-MI depression in the rat.

GPR39 Knockout Worsens Microcirculatory Response to Experimental Stroke in a Sex-Dependent Manner.

No current treatments target microvascular reperfusion after stroke, which can contribute to poor outcomes even after successful clot retrieval. The G protein-coupled receptor GPR39 is expressed in brain peri-capillary pericytes, and has been implicated in microvascular regulation, but its role in stroke is unknown. We tested the hypothesis that GPR39 plays a protective role after stroke, in part due to preservation of microvascular perfusion. We generated GPR39 knockout (KO) mice and tested whether GPR39 gene deletion worsens capillary blood flow and exacerbates brain injury and functional deficit after focal cerebral ischemia. Stroke was induced in male and female GPR39 KO and WT littermates by 60-min middle cerebral artery occlusion (MCAO). Microvascular perfusion was assessed via capillary red blood cell (RBC) flux in deep cortical layers in vivo using optical microangiography (OMAG). Brain injury was assessed by measuring infarct size by 2,3,5-triphenyltetrazolium chloride staining at 24 h or brain atrophy at 3 weeks after ischemia. Pole and cylinder behavior tests were conducted to assess neurological function deficit at 1 and 3 weeks post-stroke. Male but not female GPR39 KO mice exhibited larger infarcts and lower capillary RBC flux than WT controls after stroke. Male GPR39 KO mice also exhibited worse neurologic deficit at 1 week post-stroke, though functional deficit disappeared in both groups by 3 weeks. GPR39 deletion worsens brain injury, microvascular perfusion, and neurological function after experimental stroke. Results indicate that GPR39 plays a sex-dependent role in re-establishing microvascular flow and limiting ischemic brain damage after stroke.

GPR39 Deficiency Impairs Memory and Alters Oxylipins and Inflammatory Cytokines Without Affecting Cerebral Blood Flow in a High-Fat Diet Mouse Model of Cognitive Impairment.

Vascular cognitive impairment (VCI) is the second most common cause of dementia. There is no treatment for VCI, in part due to a lack of understanding of the underlying mechanisms. The G-protein coupled receptor 39 (GPR39) is regulated by arachidonic acid (AA)-derived oxylipins that have been implicated in VCI. Furthermore, GPR39 is increased in microglia of post mortem human brains with VCI. Carriers of homozygous GPR39 SNPs have a higher burden of white matter hyperintensity, an MRI marker of VCI. We tested the hypothesis that GPR39 plays a protective role against high-fat diet (HFD)-induced cognitive impairment, in part mediated via oxylipins actions on cerebral blood flow (CBF) and neuroinflammation. Homozygous (KO) and heterozygous (Het) GPR39 knockout mice and wild-type (WT) littermates with and without HFD for 8 months were tested for cognitive performance using the novel object recognition (NOR) and the Morris water maze (MWM) tests, followed by CBF measurements using MRI. Brain tissue and plasma oxylipins were quantified with high-performance liquid chromatography coupled to mass spectrometry. Cytokines and chemokines were measured using a multiplex assay. KO mice, regardless of diet, swam further away from platform location in the MWM compared to WT and Het mice. In the NOR test, there were no effects of genotype or diet. Brain and plasma AA-derived oxylipins formed by 11- and 15-lipoxygenase (LOX), cyclooxygenase (COX) and non-enzymatically were increased by HFD and GPR39 deletion. Interleukin-10 (IL-10) was lower in KO mice on HFD than standard diet (STD), whereas IL-4, interferon γ-induced protein-10 (IP-10) and monocyte chemotactic protein-3 (MCP-3) were altered by diet in both WT and KO, but were not affected by genotype. Resting CBF was reduced in WT and KO mice on HFD, with no change in vasoreactivity. The deletion of GPR39 did not change CBF compared to WT mice on either STD or HFD. We conclude that GPR39 plays a role in spatial memory retention and protects against HFD-induced cognitive impairment in part by modulating inflammation and AA-derived oxylipins. The results indicate that GPR39 and oxylipin pathways play a role and may serve as therapeutic targets in VCI.

Age-dependent cognitive impairment, hydrocephalus and leukocyte infiltration in transgenic mice with endothelial expression of human EPHX2.

Soluble epoxide hydrolase (sEH) is upregulated in microvascular endothelium of human brain with vascular cognitive impairment (VCI). Transgenic endothelial expression of human sEH in mice (Tie2hsEH) induces endothelial dysfunction (ED), a pathogenetic mechanism of VCI. We sought to determine if endothelial upregulation of sEH is sufficient to cause cognitive impairment, and if cognitive impairment due to chronic hypoperfusion induced by unilateral common carotid artery occlusion (CCAO) is exacerbated in Tie2hsEH mice. Behavioral performance was assessed by the open field, rotarod, novel object, Morris water maze and fear conditioning tests. Cerebral blood flow and brain morphology were evaluated by MRI, and inflammatory changes investigated using immunohistochemistry and flow cytometry. We demonstrate that transgenic endothelial expression of sEH is sufficient to induce cognitive impairment, associated with leukocyte infiltration, brain atrophy and accelerated, age-dependent ventriculomegaly, identifying ED and sEH upregulation as potential underlying mechanisms and therapeutic targets for VCI.

Pretreatment with pentoxifylline has antidepressant-like effects in a rat model of acute myocardial infarction.

We have observed that, after myocardial infarction (MI), rats display apoptosis in the limbic system that can be prevented by pentoxifylline (PTX), a proinflammatory cytokine inhibitor. We have hypothesized that reduction of apoptosis in the limbic system can attenuate the depressive behaviour occurring post-MI. The present study was, therefore, designed to assess the outcome of PTX on depressive behaviour manifesting after MI. Myocardial ischaemia, induced for 40 min in male Sprague-Dawley rats, was followed by reperfusion (MI groups). Sham groups were subjected to the same protocol without occlusion. PTX (10 mg/kg/day) or saline was administered intraperitoneally 15 min before ischaemia, and then every day until sacrifice. Two weeks after ischaemia, depression was evaluated by the forced swim test and the sucrose preference test. At the end of the experiment, the animals were sacrificed, and myocardial infarct size was examined along with plasma IL-1ß concentrations. MI rats drank less sucrose in the sucrose preference test and were more immobile in the forced swim test than the sham controls. PTX reversed these behaviours in the MI group to a level similar to that in the untreated sham group, without affecting infarct size. PTX reduced plasma IL-1ß concentrations in both sham and MI rats. We conclude that PTX administration significantly reverses the depressive-like behaviour seen after MI in rats.

GPR39 localization in the aging human brain and correlation of expression and polymorphism with vascular cognitive impairment.

INTRODUCTION: The pathogenesis of vascular cognitive impairment (VCI) is not fully understood. GPR39, an orphan G-protein coupled receptor, is implicated in neurological disorders but its role in VCI is unknown. METHODS: We performed GPR39 immunohistochemical analysis in post mortem brain samples from mild cognitive impairment (MCI) and control subjects. DNA was analyzed for GPR39 single nucleotide polymorphisms (SNPs), and correlated with white matter hyperintensity (WMH) burden on pre mortem magnetic resonance imaging. RESULTS: GPR39 is expressed in aged human dorsolateral prefrontal cortex, localized to microglia and peri-capillary cells resembling pericytes. GPR39-capillary colocalization, and density of GPR39-expressing microglia was increased in aged brains compared to young. SNP distribution was equivalent between groups; however, homozygous SNP carriers were present only in the MCI group, and had higher WMH volume than wild-type or heterozygous SNP carriers. DISCUSSION: GPR39 may play a role in aging-related VCI, and may serve as a therapeutic target and biomarker for the risk of developing VCI.

Paradoxical sleep insomnia and decreased cholinergic neurons after myocardial infarction in rats.

STUDY OBJECTIVES: Acute myocardial infarction (MI) is followed, within a few hours, by neuronal loss in the central nervous system (CNS), including the limbic system, the hypothalamus, and the brainstem. Sleep before and after MI was investigated in the first experiment. In a parallel experiment, 2 weeks after MI, we quantified brainstem cholinergic neurons known to control paradoxical sleep (PS). MEASUREMENTS AND RESULTS: Data were obtained from 28 adult male Sprague-Dawley rats weighing 350-375 g and maintained under a 12-12 light-dark cycle in 2 experiments on 16 and 12 rats, respectively. The 16 animals in the first experiment were implanted with chronic electroencephalographic (EEG) and electromyographic (EMG) electrodes. A week after surgery, these animals were habituated for 2 days to the recording equipment, and baseline sleep was charted for 24 h. The next morning, MI was induced in 8 rats by occluding the left anterior descending coronary artery for 40 min. The remaining 8 rats served as sham-operated controls. Sleep was recorded again 2 weeks after MI. The number of choline acetyltransferase (ChAT)-positive neurons was counted in the second, parallel experiment on 6 MI and 6 sham rats. Compared to the sham controls, MI rats displayed longer latency to sleep onset, shorter latency to paradoxical sleep (PS), and curtailed PS duration. The number of ChAT-positive neurons in the pedunculopontine tegmentum (PPT) area of MI rats was significantly decreased compared to the sham controls, while the number of laterodorsal tegmentum (LDT) cholinergic neurons was not different. CONCLUSION: Acute MI is accompanied, within 2 weeks, by PS-specific insomnia that can be explained, at least partly, by a specific loss of cholinergic neurons in an area known to control PS.

Chronic pretreatment with celecoxib reduces infarct size.

This study was designed to evaluate the effect of long-term pretreatment with celecoxib, a cyclooxygenase-2 inhibitor, on myocardial infarct size. Celecoxib (3 mg/kg/day i.p; n = 16) or vehicle (DMSO 50%; EtOH 15%; distilled water, n = 16) was administered chronically to male Sprague-Dawley rats through ALZET osmotic pumps for 28 days. Under anaesthesia, the animals were then subjected to left anterior descending coronary artery occlusion for 40 minutes, followed by 24-hour reperfusion. The results show that myocardial infarct size in celecoxib-treated rats was significantly reduced compared to the control group (37.5 +/- 2.5% versus 48.0 +/- 2.6% of the area at risk, P < 0.05, n = 10 per group). Accumulation of neutrophils, estimated by myeloperoxidase levels, indicated an increase in the ischemic area without any significant difference between groups. No significant difference was observed between the treated and vehicle groups in terms of plasma prostaglandin E2 and tumour necrosis factor-alpha. Apoptosis, evaluated by Bax/Bcl-2 and terminal dUTP nick-end labelled-positive cells, was significantly decreased in the subendocardial layer of the ischemic area in celecoxib-treated rats. This study indicates that pretreatment with celecoxib can reduce infarct size by a mechanism, which may involve apoptosis inhibition.

Lactobacillus helveticus and Bifidobacterium longum taken in combination reduce the apoptosis propensity in the limbic system after myocardial infarction in a rat model.

Myocardial infarction (MI) stimulates the release of pro-inflammatory substances that induce apoptosis in the limbic system. Pro-inflammatory cytokines are considered as the root cause of apoptosis, although the mechanism is not fully explained and/or understood at this time. In addition, depression may induce gastrointestinal perturbations that maintain the elevated levels of pro-inflammatory cytokines. It has been shown that some specific probiotic formulations may reduce gastrointestinal problems induced by stress and the pro/anti-inflammatory cytokine ratio. Therefore, we hypothesised that probiotics, when given prophylactically, may diminish the apoptosis propensity in the limbic system following a MI. Male adult Sprague-Dawley rats were given probiotics (Lactobacillus helveticus and Bifidobacterium longum in combination) or placebo in their drinking-water for four consecutive weeks. A MI was then induced in the rats by occluding the left anterior coronary artery for 40 min. Rats were killed following a 72 h reperfusion period. Infarct size was not different in the two groups. Bax/Bcl-2 (pro-apoptotic/anti-apoptotic) ratio and caspase-3 (pro-apoptotic) activity were reduced in the amygdala (lateral and medial), as well as in the dentate gyrus in the probiotics group when compared with the placebo. Akt activity (anti-apoptotic) was increased in these same three regions. No significant difference was observed in Ca1 and Ca3 for the different markers measured. In conclusion, the probiotics L. helveticus and B. longum, given in combination as preventive therapy, reduced the predisposition of apoptosis found in different cerebral regions following a MI.

Sleep as a Therapeutic Target in the Aging Brain.

Sleep is a behavioral phenomenon conserved among mammals and some invertebrates, yet the biological functions of sleep are still being elucidated. In humans, sleep time becomes shorter, more fragmented, and of poorer quality with advancing age. Epidemiologically, the development of age-related neurodegenerative diseases such as Alzheimer's and Parkinson's disease is associated with pronounced sleep disruption, whereas emerging mechanistic studies suggest that sleep disruption may be causally linked to neurodegenerative pathology, suggesting that sleep may represent a key therapeutic target in the prevention of these conditions. In this review, we discuss the physiology of sleep, the pathophysiology of neurodegenerative disease, and the current literature supporting the relationship between sleep, aging, and neurodegenerative disease.

Patterns and risk factors of birth defects in rural areas of south-eastern Gabon.

Within the context of high neonatal mortality in sub-Saharan Africa, a retrospective study was conducted on the prevalence of congenital malformations and the association between maternal risk factors and birth defects in rural populations of south-eastern Gabon. Two populations were studied: a group of 3500 births recorded in rural area (Koula-Moutou) and a second group of 4212 births in a semi-rural area (Franceville) in Gabon. Our data showed an increasing prevalence in congenital anomalies from rural to urban areas (P < 0.001). Maternal risk factors such as age > 35 years, multiparity and employment status were significantly associated with the levels of stillbirth. Together with abortions and stillbirths, congenital malformations require strong monitoring in rural and urban areas of sub-Saharan Africa.

The Prevalence of HIV in Cancer Patients at the Surgical Oncology Unit of Donka University Hospital of Conakry (Guinea).

Aim. To determine the prevalence of HIV infection among patients seen at the surgical oncology unit of Donka (Conakry, Guinea). Method. We conducted a retrospective and descriptive study of HIV infection in cancer patients from May 2007 to December 2012. Social characteristics (age, gender, marital status, and education) and immune status (HIV type, CD4 count) were reviewed. Results. Out of 2598 cancer patients, 54 (2.1%) tested positive for HIV. There were 11 (20.4%) defining AIDS and 43 (79.6%) nondefining AIDS cancers. The most frequent cancers were breast (14) (26.0%), non-Hodgkin lymphoma (6) (11.1%), liver (6) (11.1%), eye and annexes (6) (11.1%), and cervical cancer (5) (9.3%). These patients were female in 34 (63.0%) and had a median age of 39 years and body mass index was 20,3 Kg/m(2). They were unschooled in 40 (74.1%) and married in 35 (64.8%). CD4 count showed a median of 317 cells/mL. Antiretroviral treatment was performed in 40 (74.1%). Conclusion. HIV prevalence is higher in patients in our unit of surgical oncology. Breast cancer was the most common in this association. A national survey of a large sample is needed to determine the true prevalence and impact of HIV on cancer prognosis.

Escitalopram reduces circulating pro-inflammatory cytokines and improves depressive behavior without affecting sleep in a rat model of post-cardiac infarct depression.

Myocardial infarction (MI) in rats is followed by a behavioral syndrome similar to human post-MI depression. We tested the effects of escitalopram, a selective serotonin reuptake inhibitor, on this syndrome. MI was induced in 19 Sprague-Dawley rats by occluding the left anterior descending coronary artery for 40min, followed by reperfusion. A sham-operated group of 20 rats was submitted to the same protocol without coronary artery occlusion. Fifteen minutes after the onset of reperfusion, escitalopram (10mg/kg/day, i.p.) or saline was infused continuously through osmotic minipumps. After 2weeks of treatment, the rats were tested for behavioral despair and anhedonia by the forced swimming and sucrose preference tests, respectively. They were then sacrificed, and blood levels of pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α), PGE(2) and corticosterone were measured. In a separate cohort of 24 rats, sleep was recorded after 2weeks of post-MI treatment with escitalopram or saline. In MI rats, behavioral despair and anhedonia were blocked by escitalopram but prolonged sleep latency, low total sleep time and short latency to paradoxical sleep (PS) were not; escitalopram decreased PS in sham controls. Plasma TNF-α, PGE(2), and corticosterone levels were higher in MI rats than in the controls. Escitalopram lowered TNF-α, IL-1ß, and PGE(2) levels in both groups of rats while IL-6 showed no differences whatsoever. Escitalopram reverses post-MI behavioral syndrome in rats through a mechanism that could involve a reduction of pro-inflammatory cytokines and PGE(2). It has limited effects on sleep disorders in MI rats but reduces PS in control rats.