Vanadium administration ameliorates cortical structural and functional changes in juvenile hydrocephalic mice.

Vanadium is a prevalent neurotoxic transition metal with therapeutic potentials in some neurological conditions. Hydrocephalus poses a major clinical burden in neurological practice in Africa. Its primary treatment (shunting) has complications, including infection and blockage; alternative drug-based therapies are therefore necessary. This study investigates the function and cytoarchitecture of motor and cerebellar cortices in juvenile hydrocephalic mice following treatment with varying doses of vanadium. Fifty juvenile mice were allocated into five groups (n = 10 each): controls, hydrocephalus-only, low- (0.15 mg/kg), moderate- (0.3 mg/kg), and high- (3.0 mg/kg) dose vanadium groups. Hydrocephalus was induced by the intracisternal injection of kaolin and sodium metavanadate administered by intraperitoneal injection 72hourly for 28 days. Neurobehavioral tests: open field, hanging wire, and pole tests, were carried out to assess locomotion, muscular strength, and motor coordination, respectively. The cerebral motor and the cerebellar cortices were processed for cresyl violet staining and immunohistochemistry for neurons (NeuN) and astrocytes (glial fibrillary acidic protein). Hydrocephalic mice exhibited body weight loss and behavioral deficits. Horizontal and vertical movements and latency to fall from hanging wire were significantly reduced, while latency to turn and descend the pole were prolonged in hydrocephalic mice, suggesting impaired motor ability; this was improved in vanadium-treated mice. Increased neuronal count, pyknotic cells, neurodegeneration and reactive astrogliosis were observed in the hydrocephalic mice. These were mostly mitigated in the vanadium-treated mice, except in the high-dose group where astrogliosis persisted. These results demonstrate a neuroprotective potential of vanadium administration in hydrocephalus. The molecular basis of these effects needs further exploration.

Impaired neurogenesis with reactive astrocytosis in the hippocampus in a porcine model of acquired hydrocephalus.

BACKGROUND: Hydrocephalus is a neurological disease with an incidence of 0.3-0.7 per 1000 live births in the United States. Ventriculomegaly, periventricular white matter alterations, inflammation, and gliosis are among the neuropathologies associated with this disease. We hypothesized that hippocampus structure and subgranular zone neurogenesis are altered in untreated hydrocephalus and correlate with recognition memory deficits. METHODS: Hydrocephalus was induced by intracisternal kaolin injections in domestic juvenile pigs (43.6 ± 9.8 days). Age-matched sham controls received similar saline injections. MRI was performed to measure ventricular volume, and/or hippocampal and perirhinal sizes at 14 ± 4 days and 36 ± 8 days post-induction. Recognition memory was assessed one week before and after kaolin induction. Histology and immunohistochemistry in the hippocampus were performed at sacrifice. RESULTS: The hippocampal width and the perirhinal cortex thickness were decreased (p < 0.05) in hydrocephalic pigs 14 ± 4 days post-induction. At sacrifice (36 ± 8 days post-induction), significant expansion of the cerebral ventricles was detected (p = 0.005) in hydrocephalic pigs compared with sham controls. The area of the dorsal hippocampus exhibited a reduction (p = 0.035) of 23.4% in the hydrocephalic pigs at sacrifice. Likewise, in hydrocephalic pigs, the percentages of neuronal precursor cells (doublecortin+ cells) and neurons decreased (p < 0.01) by 32.35%, and 19.74%, respectively, in the subgranular zone of the dorsal hippocampus. The percentage of reactive astrocytes (vimentin+) was increased (p = 0.041) by 48.7%. In contrast, microglial cells were found to decrease (p = 0.014) by 55.74% in the dorsal hippocampus in hydrocephalic pigs. There was no difference in the recognition index, a summative measure of learning and memory, one week before and after the induction of hydrocephalus. CONCLUSION: In untreated juvenile pigs, acquired hydrocephalus caused morphological alterations, reduced neurogenesis, and increased reactive astrocytosis in the hippocampus and perirhinal cortex.

Protective Effects of Cannabis sativa on chemotherapy-induced nausea in a rat: Involvement of CB1 receptors.

Cyclophosphamide is an anticancer and immunosuppressive agent used in the treatment of various malignancies but causing gastrointestinal distress. Cannabis sativa and its derivatives have been used for the treatment of human gastrointestinal disorders. A purpose of this study was to investigate the effect of C. sativa on nausea induced by cyclophosphamide in rats. The rats were divided into four groups (eight animals per group): Group 1: Normal control (saline i.p.). Group 2: Rats received cyclophosphamide (200 mg/kg i.p.) 3 consecutive days. Group 3 and 4: Rats received cyclophosphamide (200 mg/kg i.p.) across Days 1-7, and C. sativa (20 and 40 mg/kg s.c.) was administered on cyclophosphamide days 4-7. We examined intake of kaolin, normal food and changes in body weight, as an indicator of the emetic stimulus. Oxidative stress markers, antioxidant enzymes status, serotonin (5-HT), dopamine, noradrenaline and CB1R levels were evaluated in the intestinal homogenate. Moreover, histopathological study was performed. Results showed that C. sativa ameliorates cyclophosphamide-induced emesis by increasing in body weight and normal diet intake with a decrease in kaolin diet intake after 7 days. Moreover, C. sativa significantly decreases (serotonin) 5-HT, dopamine and noradrenaline, as well as decreasing oxidative stress and inflammation. Administration of C. sativa significantly increased the expression of CB1R in intestinal homogenate. Treatment with C. sativa also improved the histological feature of an intestinal tissue. These results suggested that C. sativa possess antiemetic, antioxidant and anti-inflammatory effects in chemotherapy-induced nausea in rats by activating CB1R.

Effects of Rikkunshi-To, a Japanese kampo medicine, on donepezil-induced gastrointestinal side effects in mice.

Donepezil, an acetylcholinesterase inhibitor, is associated with gastrointestinal symptoms, such as nausea, vomiting, and anorexia, which may affect adherence to continuous therapy. Since Rikkunshi-To, a Japanese herbal medicine, activates the ghrelin signaling pathway and promotes gastrointestinal function, it is administered to prevent gastrointestinal symptoms. We herein investigated whether donepezil-induced gastrointestinal side effects in mice are ameliorated by Rikkunshi-To and if its therapeutic efficacy is mediated by ghrelin. Since pica behavior, the ingestion of kaolin, correlates with nausea and vomiting in humans, donepezil was intraperitoneally administered with or without Rikkunshi-To daily to mice, and food and kaolin intakes were monitored. The effects of donepezil on intestinal motility and a ghrelin receptor antagonist on donepezil-induced pica behavior, anorexia, and changes in intestinal motility were examined in mice treated with Rikkunshi-To. Pica behavior and anorexia were significantly induced by donepezil and significantly inhibited by Rikkunshi-To. Intestinal motility was significantly suppressed by donepezil and promoted by Rikkunshi-To. Furthermore, the therapeutic effects of Rikkunshi-To were antagonized by the ghrelin receptor antagonist. The present results support the therapeutic efficacy of Rikkunshi-To against donepezil-induced gastrointestinal side effects.

Probing Caffeine Administration as a Medical Management for Hydrocephalus: An Experimental Study.

BACKGROUND: Hydrocephalus is currently managed by cerebrospinal fluid diversion from the cerebral ventricles to other body sites, but this is complicated by obstruction and infection in young infants, thus adding to morbidity and mortality. Studies have reported caffeine to be a pleiotropic neuroprotective drug in the developing brain due to its antioxidant, anti-inflammatory, and antiapoptotic properties, with improved white matter microstructural development. In this study, we investigate the use of caffeine administration as a possible means of pharmacological management for hydrocephalus. METHODS: A total of 76 three-day-old mice pups from 10 dams were divided into four groups: hydrocephalus was induced in the pups in two groups by intracisternal injection of kaolin suspension, and their dams were given either caffeine (50 mg/kg by gavage) or water daily for 21 days; the dams in the other 2 (non-hydrocephalic) groups similarly had either caffeine or water; the pups received caffeine administered via lactation. Developmental neurobehavioral tests were performed until day 21, when the pups were sacrificed. Their brains were removed and processed for Cresyl and Golgi staining; both quantitative and qualitative analyses were then carried out. RESULTS: Improved developmental motor activities and reflexes were observed in the hydrocephalus + caffeine-treated pups. Caffeine administration was associated with reduced cell death and increased dendritic arborization of the neurons in the sensorimotor cortex and striatum of hydrocephalic mice pups. CONCLUSION: Caffeine administration appears to have promise as an adjunct in hydrocephalus management, and its use needs to be further explored.

Reactive microglia and mitochondrial unfolded protein response following ventriculomegaly and behavior defects in kaolin-induced hydrocephalus.

Ventriculomegaly induced by the abnormal accumulation of cerebrospinal fluid (CSF) leads to hydrocephalus, which is accompanied by neuroinflammation and mitochondrial oxidative stress. The mitochondrial stress activates mitochondrial unfolded protein response (UPRmt), which is essential for mitochondrial protein homeostasis. However, the association of inflammatory response and UPRmt in the pathogenesis of hydrocephalus is still unclear. To assess their relevance in the pathogenesis of hydrocephalus, we established a kaolin-induced hydrocephalus model in 8-week-old male C57BL/6J mice and evaluated it over time. We found that kaolin-injected mice showed prominent ventricular dilation, motor behavior defects at the 3-day, followed by the activation of microglia and UPRmt in the motor cortex at the 5-day. In addition, PARP-1/NF-κB signaling and apoptotic cell death appeared at the 5-day. Taken together, our findings demonstrate that activation of microglia and UPRmt occurs after hydrocephalic ventricular expansion and behavioral abnormalities which could be lead to apoptotic neuronal cell death, providing a new perspective on the pathogenic mechanism of hydrocephalus. [BMB Reports 2022; 55(4): 181-186].

Neurobehavioural changes and morphological study of cerebellar purkinje cells in kaolin induced hydrocephalus.

Cerebellar abnormalities are commonly associated with hydrocephalus. However, the effect of hydrocephalus on the otherwise normal cerebellum has been largely neglected. This study assesses the morphological changes in the Purkinje cells in relation to cerebellar dysfunction observed in juvenile hydrocephalic rats. Fifty-five three-week old albino Wistar rats were used, hydrocephalus was induced by intracisternal injection of kaolin (n = 35) and others served as controls (n = 20). Body weight measurements, hanging wire, negative geotaxis, and open field tests were carried out at the onset and then weekly for 4 weeks, rats were killed, and their cerebella processed for Hematoxylin and Eosin, Cresyl violet and Golgi staining. Qualitative and quantitative studies were carried out; quantitative data were analyzed using two-way ANOVA and independent T tests at p < 0.05. Hydrocephalic rats weighed less than controls (p = 0.0247) but their cerebellar weights were comparable. The hydrocephalic rats had a consistently shorter latency to fall in the hanging wire test (F(4,112) = 18.63; p < 0.0001), longer latency to turn in the negative geotaxis test (F(4,112) = 22.2; p < 0.0001), and decreased horizontal (F(4,112) = 4.172, p = 0.0035) and vertical movements (F(4,112) = 4.397; p = 0.0024) in the open field test than controls throughout the 4 weeks post-induction. Cellular compression in the granular layer, swelling of Purkinje cells with vacuolations, reduced dendritic arborization and increased number of pyknotic Purkinje cells were observed in hydrocephalic rats. Hydrocephalus caused functional and morphological changes in the cerebellar cortex. Purkinje cell loss, a major pathological feature of hydrocephalus, may be responsible for some of the motor deficits observed in this condition.

Health Risk Evaluation of Trace Elements in Geophagic Kaolinitic Clays within Eastern Dahomey and Niger Delta Basins, Nigeria.

The deliberate consumption of earthly materials is a universally recognised habit with health benefits and risks to those that practice it. Thirteen (13) samples comprising of six (6) Cretaceous and seven (7) Paleogene/Neogene geophagic kaolinitic materials, respectively, were collected and analysed for trace element concentrations (V, Cr, Co, Ni, Zn, Pb, and Fe), and possible risk on consumers' health. The trace element compositions were obtained using laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS) and X-ray fluorescence spectrometry (XRF) analytical methods. Based on their average concentrations, Fe > V > Cr > Ni > Zn > Pb > Cu > Co and Fe > V > Cr > Zn > Cu > Pb > Ni > Co for the Cretaceous and Paleogene/Neogene geophagic clays, respectively. Iron concentrations were significantly higher in Paleogene/Neogene geophagic clays than in Cretaceous geophagic clays. The nutritional value of Cu and Zn were lower whereas, Cr and Fe were higher than the recommended dietary intake. The index of geoaccumulation (0 < Igeo ≤ 1) showed that the geophagic materials were uncontaminated to moderately contaminated by the trace elements. The overall hazard indices (HI) for non-carcinogenic effects showed that the geophagic clays pose threat to children (HI > 1) and no threat to adults (HI < 1) health. However, the carcinogenic risk indices (CRI) for Cr, Ni, and Pb were within acceptable cancer risks (10-6 < CRI < 10-4) for children and adults. Hence, based on the trace element s HI and CRI, this study concluded that the consumption of Cretaceous and Paleogene/Neogene geophagic kaolinitic clays poses no risks to adult health but children might suffer health risk if the geophagic clays are not beneficiated before ingestion.

Kaolin-induced hydrocephalus causes acetylcholinesterase activity dysfunction following hypothalamic damage in infant rats.

In hydrocephalus, the progressive accumulation of cerebrospinal fluid (CSF) causes dilatation of the lateral ventricles affecting the third ventricle and diencephalic structures such as the hypothalamus. These structures play a key role in the regulation of several neurovegetative functions by the production of the hormones. Since endocrine disturbances are commonly observed in hydrocephalic children, we investigated the impact of progressive ventricular dilation on the hypothalamus of infant rats submitted to kaolin-induced hydrocephalus. Seven-day-old infant rats were submitted to hydrocephalus induction by kaolin 20% injection method. After 14 days, the animals were decapitated and brain was collected to analyze mitochondrial function, neuronal activity by acetylcholinesterase (AChE) enzyme, oxidative damage, glial activation, and, neurotransmission-related proteins and anti-apoptotic processes in the hypothalamus. The hydrocephalic animals showed reduction in respiratory rates in the States of phosphorylation (P < 0.01) and non-phosphorylation (P < 0.05); increase in AChE activity in both the cytosol (P < 0.05) and the membrane (P < 0.01); decrease in synaptophysin (P < 0.05) and Bcl-2 (P < 0.05) contents and; increase in protein carbonyl (P < 0.01), GFAP (P < 0.01) and Iba-1 (P < 0.05) levels. The results demonstrate that ventricular dilation causes hypothalamic damage characterized by cholinergic dysfunction and suggests further investigation of the synthesis and secretion of hormones to generate new approaches and to assist in the treatment of hydrocephalic patients with hormonal alterations.

High prevalence of kaolin consumption in migrant women living in a major urban area of France: A cross-sectional investigation.

Geophagia is a feeding behavior involving the regular intake of soil, including clay-like kaolin. Frequent in Africa, kaolin consumption is associated with heavy metal intoxication, iron and other micronutrient deficiencies, geohelminth infection and inactivation of concomitantly taken drugs. It is expected that this practice would be imported into an asylum country during the immigration process. To confirm this hypothesis, a single center, cross-sectional study was conducted at the University Hospital of Nantes, France, whose main objective was to assess whether the prevalence of kaolin consumers was high in a migrant population living in a large French metropolitan area (the city of Nantes). Each woman consulting for the first time at the Medical and Psychosocial Gynecology Obstetric Unit during the inclusion period ranging from January 1, 2017, to July 1, 2017, was asked for consent to be included in the study. The main outcome was the proportion of positive answers regarding consumption of kaolin within the last twelve months, with its 95% confidence interval (CI). A logistic regression was performed to identify drivers of consumption, and a clustering approach was conducted to identify profiles of consumers. A total of 284 women were included in the study, of whom 110 (38.7%) were pregnant. Our main finding was a 14.1% (95% CI: 10.5-18.6) prevalence of clay consumers. Second, the characteristic most strongly associated with consumption was Central or West Africa origin (adjusted Odds Ratio (aOR) = 52.7; 95% CI: 13.7-202.2). Finally, 60% of consumers showed signs of addictive-like phenomena, and three profiles were identified, depicting a continuum of patients in regard to their control over their kaolin consumption. Our results suggest that kaolin consumption is frequent in particular subpopulations of migrants. This warrants further study of the clinical consequences of kaolin consumption and its associated addictive-like symptoms.

Severe craving associated with kaolin consumption.

PURPOSE: Kaolin eating is an ancestral and worldwide tradition, particularly in women in order to relieve nauseas and abdominal troubles. Nevertheless, damaging effects such as anemia and intestinal troubles are well documented. However, compulsive disorders associated with kaolin intake are less known. RESULT: We reported in this paper a severe craving observed in a young woman consuming kaolin for several years, associated with a microcytic iron-deficiency non-regenerative anemia. CONCLUSION: This paper allows to draw attention among physicians who are rarely informed of this practice imported from abroad and have consequently a limited role in informing patients of the potential deleterious side effects of geophagia.

Death of a Female Prostitute Due to Intestinal Obstruction by an Unknown Substance.

A young adult black female, known to be a prostitute and suspected of smuggling narcotics, was found dead in her apartment in a state of early decomposition. Oval-shaped gray-white masses of exogenous origin protruded from the anus. The autopsy showed dilatation of the folds of the large intestine, which were almost completely filled with these oval-shaped gray-white masses of foreign material. The uterus was enlarged with multiple large leiomyomas. Toxicological tests of blood and the foreign material revealed no toxicologically relevant substances. Kaolin was detected in a sample of the foreign material from the large intestine. The immediate cause of death was intestinal obstruction due to the formation of a kaolin bezoar with simultaneous compression of the large intestine by the enlarged myomatous uterus. Subsequent revelation of a habit the deceased had brought from her native country led to the conclusion that this exotic custom was responsible for her death.

In vitro effects of a kaolin-coated hemostatic dressing on anticoagulated blood.

BACKGROUND: The use of kaolin-coated dressings has become common and have efficacy in normal patients, but their increased use will inevitably include use on bleeding patients taking anticoagulants. We hypothesize that kaolin coating material (KCM) will improve clotting regardless of anticoagulation medication. METHODS: A prospective study was performed on blood from patients who were on a vitamin K antagonist (VKA), unfractionated heparin (UH), an antiplatelet (AP) agent, a Xa inhibitor (Xa), or a direct thrombin inhibitor (DTI). None were on more than one type of anticoagulation medication. Viscoelastic testing was performed with and without KCM. All p values were adjusted for multiple comparisons. RESULTS: The addition of KCM significantly decreased the time for initial clot formation (CT) in all groups. The mean CT for controls was decreased from 692 to 190.8 s (p < 0.0001). KCM decreased the initial clot formation time by about 1.5 times in those on DTI (p = 0.043) and 2.5 times in those taking AP medication (p < 0.001). The most profound effect was seen in those on UH (no KCM 1,602 s vs. KCM 440 s; p < 0.001), VKA (no KCM 1,152 s vs. 232 s; p < 0.01), and Xa (no KCM 1,342 s vs. 287 s; p < 0.001). Analysis of other clot formation parameters revealed that KCM significantly improved the clot formation kinetics (CFT) only in patients taking Xa (p = 0.03). KCM improved maximum clot strength in patients on Xa inhibitors (p = 0.05). Patients on UH had a larger effect size with an increase in clot strength from 24.35 mm to 43.35 mm whereas those on Xa had an increase of 38.7 mm to 49.85 mm. CONCLUSION: In this in vitro analysis, the addition of KCM to the blood of patients taking any of these anticoagulation medications significantly improved the time to initial clot formation, indicating that kaolin-based hemostatic dressings will be effective in initiating clot formation in patients on anticoagulants. LEVEL OF EVIDENCE: Therapeutic, level IV.

Melatonin Attenuates Histopathological Changes in the Hippocampus of Infantile Rats with Kaolin-Induced Hydrocephalus.

OBJECTIVE/AIM: Hydrocephalus is defined as an incapacitating neurological disorder characterized by ventricular enlargement in children, but the effects of melatonin on this hydrocephalus have not yet been fully elucidated. In the present experiment, we attempted to investigate the effects of exogenous melatonin administration on hydrocephalus-induced hippocampal changes in infantile rats. METHODS: In this study, we randomly divided 45 Swiss albino rats aged 2 weeks into 3 groups: group I, the control group received a sham injection with needle insertion only; groups II and III were given kaolin injections before treatment - group II, the hydrocephalus group, was treated with an isotonic NaCl solution, and group III, the hydrocephalus plus melatonin group, was treated with 0.5 mg/100 g body weight of exogenous melatonin. Both immunohistochemical and histological analyses were performed after hydrocephalus induction and melatonin administration. Immunohistochemical staining consisted anti-glial fibrillary acidic protein staining. The TUNEL technique was used for defining quantitate apoptosis. RESULTS: Melatonin administration significantly attenuated chronic hydrocephalus-induced histopathological changes in the hippocampal subregions of infantile rats. Compared to hydrocephalic rats treated with saline solution, melatonin significantly decreased the number of apoptotic cells and pyknotic index values of each hippocampal subregion after the kaolin-induced hydrocephalus (p < 0.001). CONCLUSION: The present results demonstrate that the chronic hydrocephalus-induced histopathological changes in the hippocampus were partially reversible with melatonin treatment, suggesting its neuroprotective effects in infantile rats. However, these findings need to be confirmed by further experimental studies and clinical trials.

Myelin Sheath Injury in Kaolin-Induced Hydrocephalus: A Light and Electron Microscopy Study.

BACKGROUND: In hydrocephalus, the impairment of cognitive and motor functions is thought to be partly due to injury to the myelin sheath of axons in the central nervous system. The exact nature of this injury is not completely understood. METHODS: We induced hydrocephalus in 3-week-old rats with an intracisternal injection of kaolin suspension (0.04 ml of 200 mg/ml) and examined paraffin and ultrathin sections of the subcortical white matter from coronal slices of the cerebrum obtained at the level of the optic chiasm after sacrifice at weekly intervals for 4 weeks. RESULTS: Over time, there was a progression of injury to the myelin sheath consisting of attenuation, lamella separation and accumulation of myelin debris, focal degeneration, and the appearance of casts and loops. CONCLUSION: The results suggest that myelin injury in kaolin-induced hydrocephalus progresses with the duration and severity of ventriculomegaly.

A comparative study of tissue factor and kaolin on blood coagulation assays using rotational thromboelastometry and thromboelastography.

Rotational thromboelastometry (ROTEM) and thromboelastography (TEG) have been increasingly used to diagnose acute coagulopathy and guide blood transfusion. The tests are routinely performed using different triggering activators such as tissue factor and kaolin, which activate different pathways yielding different results. To optimize the global blood coagulation assays using ROTEM and TEG, we conducted a comparative study on the activation methods employing tissue factor and kaolin at different concentrations as well as standard reagents as recommended by the manufacturer of each device. Key parameter values were obtained at various assay conditions to evaluate and compare coagulation and fibrinolysis profiles of citrated whole blood collected from healthy volunteers. It was found that tissue factor reduced ROTEM clotting time and TEG R, and increased ROTEM clot formation time and TEG K in a concentration-dependent manner. In addition, tissue factor affected ROTEM alpha angle, and maximum clot firmness, especially in the absence of kaolin activation, whereas both ROTEM and TEG clot lysis (LI30, CL30, and LY30) remained unaffected. Moreover, kaolin reduced ROTEM clotting time and TEG R and K, but to a lesser extent than tissue factor, in-tem and ex-tem. Correlations in all corresponding parameters between ROTEM and TEG were observed, when the same activators were used in the assays compared with lesser correlations between standard kaolin TEG and ROTEM (INTEM/EXTEM). The two types of viscoelastic point-of-care devices provide different results, depending on the triggering reagent used to perform the assay. Optimal assay condition was obtained to reduce assay time and improve assay accuracy.

Effect of Hautriwaic Acid Isolated from Dodonaea viscosa in a Model of Kaolin/Carrageenan-Induced Monoarthritis.

In the present work, the antiarthritic activity of hautriwaic acid is reported. This ent-clerodane diterpene isolated from Dodonaea viscosa was evaluated in mice using a kaolin/carrageenan-induced monoarthritis model. The inflammation observed in the joint (knee) on days 1-8 ranged from 50-70 %. After 10 days of treatment with different doses of hautriwaic acid (5, 10, 20 mg/kg), a decrease in knee inflammation was detected. This recovery was observed with both reference drugs, methotrexate (1 mg/kg) and diclofenac (0.75 mg/kg). In these groups of mice, the concentration of proinflammatory cytokines interleukin-1 beta, interleukin-6, and tumor necrosis factor alpha in the joint was significantly lower than that of the negative control group (animals with damage without any treatment). The negative control group presented a decrease in the concentration of interleukin-10, while the groups that received hautriwaic acid at different dose exhibited an increase in this interleukin. This anti-inflammatory cytokine was not modified in the joint of mice with diclofenac, but in mice that received methotrexate, a significant decrease was observed. Hautriwaic acid isolated from D. viscosa diminished the joint edema induced by this mixture of polysaccharides (carrageenan), possibly by acting as immunomodulator of the inflammatory response.

A role of supraspinal galanin in behavioural hyperalgesia in the rat.

INTRODUCTION: In chronic pain disorders, galanin (GAL) is able to either facilitate or inhibit nociception in the spinal cord but the contribution of supraspinal galanin to pain signalling is mostly unknown. The dorsomedial nucleus of the hypothalamus (DMH) is rich in galanin receptors (GALR) and is involved in behavioural hyperalgesia. In this study, we evaluated the contribution of supraspinal GAL to behavioural hyperalgesia in experimental monoarthritis. METHODS: In Wistar-Han males with a four week kaolin/carrageenan-induced monoarthritis (ARTH), paw-withdrawal latency (PWL) was assessed before and after DMH administration of exogenous GAL, a non-specific GALR antagonist (M40), a specific GALR1 agonist (M617) and a specific GALR2 antagonist (M871). Additionally, the analysis of c-Fos expression after GAL injection in the DMH was used to investigate the potential involvement of brainstem pain control centres. Finally, electrophysiological recordings were performed to evaluate whether pronociceptive On- or antinociceptive Off-like cells in the rostral ventromedial medulla (RVM) relay the effect of GAL. RESULTS: Exogenous GAL in the DMH decreased PWL in ARTH and SHAM animals, an effect that was mimicked by a GALR1 agonist (M617). In SHAM animals, an unselective GALR antagonist (M40) increased PWL, while a GALR2 antagonist (M871) decreased PWL. M40 or M871 failed to influence PWL in ARTH animals. Exogenous GAL increased c-Fos expression in the RVM and dorsal raphe nucleus (DRN), with effects being more prominent in SHAM than ARTH animals. Exogenous GAL failed to influence activity of RVM On- or Off-like cells of SHAM and ARTH animals. CONCLUSIONS: Overall, exogenous GAL in the DMH had a pronociceptive effect that is mediated by GALR1 in healthy and arthritic animals and is associated with alterations of c-Fos expression in RVM and DRN that are serotonergic brainstem nuclei known to be involved in the regulation of pain.

Topic usage of kaolin-impregnated gauze as a hemostatic in tonsillectomy.

BACKGROUND: The main postoperative complications after tonsillectomy are due to bleeding, and effective hemostasis may lead to a reduction of overall postoperative morbidity. This study was undertaken to determine the efficacy and safety of a novel kaolin-based hemostatic dressing in tonsillectomy. METHODS: A pilot, single-blind, open label study was performed in patients aged 3-20 y with history of chronic or hypertrophic tonsillitis. Cold dissection tonsillectomy (CDT) + ligature was performed by the same surgeon. Hemostasis on each tonsillar fossa was achieved using kaolin-impregnated gauze (KG; study group) or standard surgical cotton gauze (CG; control). Time to complete hemostasis, operative time, intraoperative blood loss, pain score, analgesic use, and return to normal diet and activity were recorded for all children. RESULTS: A total of 230 patients with a mean age of 8.0 y (138 in the study group and 92 in the control group) were included in the study. Both operative time and intraoperative blood loss were significantly reduced in the KG group (P < 0.0001) versus the CG group. At 5 min, 84.8% patients using the KG successfully achieved complete hemostasis versus 34.8% in the CG group where standard gauze controlled bleeding only partially. Results show significantly less pain for the KG group at 6- and 12-h postoperative when compared with the CG group (P < 0.0001). Also, the KG group required less analgesic medications, returned to normal diet and normal activities faster than the CG group (P < 0.01). CONCLUSIONS: Preliminary findings show that the KG is effective and safe in managing surgical bleeding after tonsillectomy. In addition to rapid bleeding control, the dressing causes minimal inflammation and pain and allows patients to quickly return to normal activities. This novel dressing is a promising tool for ear, nose and throat surgical hemostasis.

Fluctuating anaemia in treated HIV patients: could be a PICA?

HIV infected patients are frequently exposed to anaemia, due to antiretroviral agents and/or prophylactic treatment of opportunistic infections. Anemia due to PICA, unusually evoked in our western countries, could be a more frequent situation than imagined. We report two cases of fluctuating anemia with no HIV or iatrogenic origin, observed in two HIV infected women, 47 years old and 33 years old respectively, coming from Africa and treated with antiretroviral agents. The anemia was explained by a culturally sanctioned practice of kaolin ingestion, in the broader context of PICA and resolved after the withdrawal of kaolin ingestion. PICA, and in particular kaolin ingestion, must be investigated when HIV infected patients came from Africa and presented significative unexplained anemia.