A novel model of acquired hydrocephalus for evaluation of neurosurgical treatments.

BACKGROUND: Many animal models have been used to study the pathophysiology of hydrocephalus; most of these have been rodent models whose lissencephalic cerebral cortex may not respond to ventriculomegaly in the same way as gyrencephalic species and whose size is not amenable to evaluation of clinically relevant neurosurgical treatments. Fewer models of hydrocephalus in gyrencephalic species have been used; thus, we have expanded upon a porcine model of hydrocephalus in juvenile pigs and used it to explore surgical treatment methods. METHODS: Acquired hydrocephalus was induced in 33-41-day old pigs by percutaneous intracisternal injections of kaolin (n = 17). Controls consisted of sham saline-injected (n = 6) and intact (n = 4) animals. Magnetic resonance imaging (MRI) was employed to evaluate ventriculomegaly at 11-42 days post-kaolin and to plan the surgical implantation of ventriculoperitoneal shunts at 14-38-days post-kaolin. Behavioral and neurological status were assessed. RESULTS: Bilateral ventriculomegaly occurred post-induction in all regions of the cerebral ventricles, with prominent CSF flow voids in the third ventricle, foramina of Monro, and cerebral aqueduct. Kaolin deposits formed a solid cast in the basal cisterns but the cisterna magna was patent. In 17 untreated hydrocephalic animals. Mean total ventricular volume was 8898 ± 5917 SD mm3 at 11-43 days of age, which was significantly larger than the baseline values of 2251 ± 194 SD mm3 for 6 sham controls aged 45-55 days, (p < 0.001). Past the post-induction recovery period, untreated pigs were asymptomatic despite exhibiting mild-moderate ventriculomegaly. Three out of 4 shunted animals showed a reduction in ventricular volume after 20-30 days of treatment, however some developed ataxia and lethargy, from putative shunt malfunction. CONCLUSIONS: Kaolin induction of acquired hydrocephalus in juvenile pigs produced an in vivo model that is highly translational, allowing systematic studies of the pathophysiology and clinical treatment of hydrocephalus.

Administration of cyclophosphamide to rats induces pica and potentiates 5-hydroxytryptamine synthesis in the intestine without causing severe intestinal injury.

The effects of cyclophosphamide on 5-hydroxytryptamine (5-HT) synthesis in the intestinal tissue of rats were investigated. Rats received 120 mg/kg cyclophosphamide intraperitoneally as a single administration, and kaolin and food intake was measured by an automatic monitoring apparatus. Ileal tissues were collected at either 24 or 72 h after administration. Cyclophosphamide caused a significant increase in kaolin intake at the acute and the delayed phases and was associated with a decrease in food intake, and body weight. Cyclophosphamide had no significant effect on intestinal mucosal morphology, or inducible nitric oxide synthase and cyclooxygenase-2 expression in the intestine. Cyclophosphamide significantly increased tryptophan hydroxylase 1 (TPH1) mRNA expression, number of anti-TPH antibody-positive cells, and 5-HT content in the intestine. Cyclophosphamide also significantly increased the expression of Tac1 mRNA, encoding preprotachykinin-1, which is a preprotein of substance P, and the number of anti-substance P antibody-positive cells in the intestine. Cyclophosphamide significantly increased Lgr5, Bmi1, and Atoh1 mRNA levels, which are markers for the proliferation and differentiation of stem cells. This study demonstrated that cyclophosphamide induced pica in rats, and potentiated 5-HT synthesis associated with hyperplasia of substance P-containing enterochromaffin cells without causing severe intestinal injury.

Design and Preclinical Evaluation of Chitosan/Kaolin Nanocomposites with Enhanced Hemostatic Efficiency.

In the current study, hemostatic compositions including a combination of chitosan and kaolin have been developed. Chitosan is a marine polysaccharide derived from chitins, a structural component in the shells of crustaceans. Both chitosan and kaolin have the ability to mediate a quick and efficient hemostatic effect following immediate application to injury sites, and thus they have been widely exploited in manufacturing of hemostatic composites. By combining more than one hemostatic agent (i.e., chitosan and kaolin) that act via more than one mechanism, and by utilizing different nanotechnology-based approaches to enhance the surface areas, the capability of the dressing to control bleeding was improved, in terms of amount of blood loss and time to hemostasis. The nanotechnology-based approaches utilized to enhance the effective surface area of the hemostatic agents included the use of Pluronic nanoparticles, and deposition of chitosan micro- and nano-fibers onto the carrier. The developed composites effectively controlled bleeding and significantly improved hemostasis and survival rates in two animal models, rats and rabbits, compared to conventional dressings and QuikClot® Combat Gauze. The composites were well-tolerated as demonstrated by their in vivo biocompatibility and absence of clinical and biochemical changes in the laboratory animals after application of the dressings.

Kaolinite group minerals: Applications in cancer diagnosis and treatment.

The clay minerals are characterized as important minerals due to their specific properties. One of the most important groups of the clay minerals is the kaolinite's group minerals due to their morphology, availability and range of potential applications. Halloysite and kaolinite are investigated here for their pharmaceutical applications and especially for their potential in cancer treatment. This review study is focusing on the potential applications of the kaolinite's group minerals in cancer diagnosis and monitoring, cancer treatment, the avoidance of metastasis, and the relief of cancer pains. Anticancer drug-loaded formulations based on these minerals show high potential for the treatment of various types of cancer as they have been shown to exhibit high anticancer activity in cancer cell lines and cancer animal models, high biocompatibility, low side effects, and high drug bioavailability.

Effects of deficit irrigation and kaolin application on vegetative growth and fruit traits of two early ripening apple cultivars.

BACKGROUND: Drought is one of the main serious problems for agriculture production which its intensity is increasing in many parts of the world, hence, improving water use efficiency is a main goal for sustainable agriculture. RESULTS: Growth indices including relative shoot length growth (SL), relative stem diameter increase (SD) and relative trunk cross sectional area growth (TCSA) measured at the start and end of the season decreased by reducing the irrigation level. Chlorophyll index (CI) was decreased at 70% crop evapotranspiration, however water use efficiency (WUE), leaf and fruit total phenolic content (TPC), and fruit anthocyanin content (AC) were among the traits that showed increment by water deficit stress in both cultivars. Shafi-Abadi cultivar showed to be more sensitive to the water stress than 'Golab'. Kaolin treatment improved SL, SD and CI traits, but this increase was statistically significant only for SD at 5% level. Kaolin had no significant effect on yield and water use efficiency (WUE), however, it had negative effect on yield efficiency (YE). Kaolin treatments also significantly increased fruit and leaf TPC (P < 0.01) but had no effect on leaf and fruit total antioxidant activity (AA), as well as fruit anthocyanin content (AC) and soluble proteins (SP). CONCLUSIONS: Irrigation at 85% ETc showed better results than 100% and 70% ETc levels for yield attributes. It seems that the more pronounced effect of kaolin on vegetative traits but not on the fruits, might be attributed to the early ripening and harvest time of the examined cultivars.

Comparative study of intracisternal kaolin injection techniques to induce congenital hydrocephalus in fetal lamb.

PURPOSE: Kaolin (aluminum silicate) has been used to generate hydrocephalus by direct cisterna magna injection in animal models. The aim of the present study is to compare which method of Kaolin injection into fetal cisterna magna is feasible, safer, and more effective to induce hydrocephalus in fetal lambs. METHODS: Twenty-five well-dated pregnant ewes at gestational 85-90 days (E85-90) were used to compare three different kaolin injection puncture techniques into the fetal cisterna magna. Group 1, ultrasound guidance in a maternal percutaneous transabdominal (TA); group 2, without opening the uterus in a transuterine (TU) technique; group 3, by occipital direct access after exteriorizing fetal head (EFH); and group 4, control group, was normal fetal lambs without injection. The fetal lambs were assessed using lateral ventricle diameter ultrasonographic measurements prior the kaolin injection and on the subsequent days. We analyzed the effectivity, mortality, and fetal losses to determine the best technique to create hydrocephalus in fetal lamb. RESULTS: After fetal intracisternal kaolin (2%, 1mL) injection, lateral ventricle diameters increased progressively in the three different interventional groups compared with the normal values of the control group (p ≤ 0.05). We observed that the transabdominal method had a 60% of fetal losses, considering failure of injection and mortality, compared with the 12.5% in the open group (EFH), and 0% for the transuterine group. CONCLUSIONS: Based on our study, we believe that both, open uterine (EFH) and transuterine approaches are more effective and safer than the transabdominal ultrasound-guided method to induce hydrocephalus.

Food aversion learning based on voluntary running in non-deprived rats: a technique for establishing aversive conditioning with minimized discomfort.

This article presents an experimental preparation for establishing conditioned food aversion (CFA) by voluntary wheel running in rats with laboratory chow and water freely available. In Experiment 1, unfamiliar food (raisins) was avoided by rats when they first encountered it. This neophobic food avoidance was habituated by repeated tests; the rats gradually increased their raisin consumption. However, the consumption remained suppressed in rats that accessed the raisins after wheel running. This finding implies that running yielded CFA, which suppressed consumption of the unfamiliar food rather than increasing it. Because running generated kaolin clay ingestion, which is a behavioral marker of nausea, it is suggested that the running-based CFA was mediated by weak gastrointestinal discomfort. Experiment 2 supported the claim that the suppressed consumption is due to running-based CFA by showing the specificity of food suppression. Demonstration of CFA based on voluntary activity in non-deprived rats will contribute to basic research on learning and memory as an alternative technique for studying aversive conditioning with minimized discomfort in animals.

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.

Effects of deficit irrigation and kaolin application on vegetative growth and fruit traits of two early ripening apple cultivars

BACKGROUND: Drought is one of the main serious problems for agriculture production which its intensity is increasing in many parts of the world, hence, improving water use efficiency is a main goal for sustainable agriculture. RESULTS: Growth indices including relative shoot length growth (SL), relative stem diameter increase (SD) and relative trunk cross sectional area growth (TCSA) measured at the start and end of the season decreased by reducing the irrigation level. Chlorophyll index (CI) was decreased at 70% crop evapotranspiration, however water use efficiency (WUE), leaf and fruit total phenolic content (TPC), and fruit anthocyanin content (AC) were among the traits that showed increment by water deficit stress in both cultivars. Shafi-Abadi cultivar showed to be more sensitive to the water stress than 'Golab' Kaolin treatment improved SL, SD and CI traits, but this increase was statistically significant only for SD at 5% level. Kaolin had no significant effect on yield and water use efficiency (WUE), however, it had negative effect on yield efficiency (YE). Kaolin treatments also significantly increased fruit and leaf TPC (P< 0.01) but had no effect on leaf and fruit total antioxidant activity (AA), as well as fruit anthocyanin content (AC) and soluble proteins (SP). CONCLUSIONS: Irrigation at 85% ETc showed better results than 100% and 70% ETc levels for yield attributes. It seems that the more pronounced effect of kaolin on vegetative traits but not on the fruits, might be attributed to the early ripening and harvest time of the examined cultivars.

Radial artery occlusion with a kaolin-filled pad after transradial cardiac catheterization.

Radial artery occlusion (RAO) occurs in 2% to 18% of patients after transradial access (TRA) cardiac catheterization. Using a kaolin-filled pad (QuikClot) reduces compression time during TRA and might reduce RAO. We examined the RAO risk with the kaolin-filled pad after TRA cardiac catheterization.This was a prospective cross-sectional study of 260 patients who underwent TRA cardiac catheterization in a cardiac ward of a Medical Center from 2012 to 2016. Patients were randomly assigned to 1 of 2 groups: the case group (n = 130) was postoperatively treated with a kaolin-filled pad, and the control group (n = 130) was treated with conventional hemostasis. Color duplex ultrasound was used to evaluate the 24-hour and 1-month postoperative radial artery flow velocity, diameter, patency, and RAO risk.RAO risk was not significantly different between the case and control groups after 24 hours (4.6% vs 5.4%, P = .776) or after 1 month (5.4% vs 6.1%, P = .789), regardless of whether it was a first TRA cardiac catheterization (after 24 hours [P = .153] or after 1month [P = .617], respectively) or a repeated TRA cardiac catheterization (after 24 hours [P = .754] or after 1month [P = .753], respectively).Using a kaolin-filled pad after TRA cardiac catheterization did not significantly reduce RAO risk compared with conventional hemostasis.

Targeting TRPV1 to relieve motion sickness symptoms in mice by electroacupuncture and gene deletion.

Motion sickness (MS) is an acute disorder that occurs in healthy individuals worldwide regardless of gender, age, or ethnicity. Our study used a mouse model to rule out the effects of any psychological factors related to MS and EA. Subjects were randomly separated into four groups, namely the control group (Con), motion sickness inducing group (MS), mentioning sickness inducing with electroacupuncture treatment group (EA) and motion sickness inducing only in TRPV1 knockout mice group (TRPV1-/-). The consumption of kaolin, a non-nutrient substance, was measured as a behavior observed response of an emetic reflex in a murine model. This behavior is referred to as pica behavior. Our results showed that pica behavior was observed in the MS group. Moreover, kaolin consumption in the EA group decreased to the average baseline of the control group. A similar result was observed in TRPV1 null mice. We also observed an increase of TRPV1 and related molecules in the thalamus, hypothalamic and brain stem after MS stimulation and a significant decrease in the EA and TRPV1 null groups. This is the first study to demonstrate that TRPV1 pathways are possibly associated with mechanisms of MS, and can be attended through EA or TRPV1 genetic manipulation.

Evaluation of self-injurious behavior, thermal sensitivity, food intake, fecal output, and pica after injection of three buprenorphine formulations in rats (Rattus norvegicus).

OBJECTIVE To assess effects of buprenorphine hydrochloride (BH), sustained-release buprenorphine (SRB), and high-concentration buprenorphine (HCB) formulations in healthy rats. ANIMALS 8 Sprague-Dawley rats. PROCEDURES In a crossover-design study, rats received BH (0.05 mg/kg), SRB (1.2 mg/kg), HCB (0.30 mg/kg), or 5% dextrose solution (0.2 mL/kg), SC, once. Self-injurious behavior and thermal sensitivity (hind limb withdrawal latencies) were assessed prior to injection (time 0) and 1, 4, 8, 12, and 24 hours after injection. Food intake, kaolin intake, and fecal output were measured over 12-hour light and dark periods before and after each treatment. Values were compared among treatments and time points. RESULTS Self-injurious behavior was detected with all buprenorphine treatments; scores were greater at all time points during the 12 hours after HCB and 24 hours after SRB administration than at time 0. Percentage change in hind limb withdrawal latencies from time 0 was higher with BH and HCB 1 hour after injection than at other time points. Postinjection light-period food intake was higher (BH and HCB) and dark-period food intake was lower (BH, HCB, and SRB), compared with preinjection values for the same treatments. For SRB, postinjection light-period kaolin intake was greater than the preinjection value, and postinjection light- and dark-period kaolin intake was greater than that for other treatments. CONCLUSIONS AND CLINICAL RELEVANCE Hypoalgesic effects were briefly observed after administration of BH or HCB in healthy rats; adverse effects were detected in some rats with all buprenorphine formulations. Studies comparing effects of BH, SRB, and HCB in rats undergoing surgery or other noxious stimuli are indicated to determine clinical benefits in this species.

Kaolin modulates ABA and IAA dynamics and physiology of grapevine under Mediterranean summer stress.

The foliar exogenous application of kaolin, a radiation-reflecting inert mineral, has proven to be an effective short-term climate change mitigation strategy for Mediterranean vineyards. In this work, we address the hypothesis that kaolin could improve both the hormonal dynamics and physiological responses of grapevines growing in Douro Region, northern Portugal. For this purpose, the leaf water potential, gas exchange and chlorophyll a fluorescence parameters were monitored, as well as the abscisic acid (ABA) and indole-3-acetic acid (IAA) quantification and immunolocalization were assessed. The study revealed a slight decrease in ABA and an increase in IAA in the kaolin treatment, which in turn were associated with the improvement of physiological performance. A month after spraying, kaolin improves the water potential respectively, 30% and 17% in the predawn and midday periods. Besides, plants treated with kaolin showed higher values of stomatal conductance, net CO2 assimilation rate and intrinsic water use efficiency. Kaolin also ameliorates the effective PSII efficiency (67%), as well as the maximum quantum efficiency of photosystem II and the photosynthetic electron transport rate (>73%). These results were consistent with the higher photochemical quenching and the lower non-photochemical quenching observed in treated leaves and with the better performance obtained by the JIP test parameters. Physiological and hormonal analysis confirmed that kaolin effectively enhance grapevine summer stress tolerance.

Emerging integrated nanoclay-facilitated drug delivery system for papillary thyroid cancer therapy.

Nanoclay can be incorporated into emerging dual functional drug delivery systems (DDSs) to promote efficiency in drug delivery and reduce the toxicity of doxorubicin (DOX) used for thyroid cancer treatment. This paper reports the expansion of the basal spacing of kaolinite nanoclay was expanded from 0.72 nm to 0.85 nm, which could provide sufficiently spacious site for hosting doxorubicin molecules and controlling the diffusion rate. A targeted design for papillary thyroid cancer cells was achieved by introducing KI, which is consumed by the sodium-iodide symporter (NIS). As indicated by MTT assays, confocal laser scanning microscopy and bio-TEM observations, methoxy-intercalated kaolinite (KaolinMeOH) exhibited negligible cytotoxicity against papillary thyroid cancer cells. By contrast, DOX-KaolinMeOH showed dose-dependent therapeutic effects in vitro, and KI@DOX-KaolinMeOH was found to act as a powerful targeted therapeutic drug. Furthermore, active and passive targeting strategies played a role in the accumulation of the drug molecules, as verified by an in vivo bio-distribution analysis.

Running induces nausea in rats: Kaolin intake generated by voluntary and forced wheel running.

Three experiments were conducted showing rats' pica behavior (kaolin clay intake) due to running in activity wheels. The amount of kaolin consumed was a positive function of the available time of voluntary running (20, 40, or 60 min), although this relationship was blunted by a descending (i.e., 60 â†’ 40 â†’ 20 min) test series of execution (Experiment 1). Pica was also generated by forced running in a motorized wheel for 60 min as a positive function of the speed of wheel rotations at 98, 185, or 365 m/h, independent of the order of execution (Experiment 2). Voluntary running generated more pica than did forced running at 80 m/h, although the distance travelled in the former condition was 27% lesser than that in the latter condition (Experiment 3). Because kaolin intake is regarded as a reliable measure of nausea in rats, these results show that wheel running, either voluntary or forced, induces nausea in rats.

Magnesium sulfate treatment for juvenile ferrets following induction of hydrocephalus with kaolin.

BACKGROUND: Previous work with 3-week hydrocephalic rats showed that white matter damage could be reduced by the calcium channel antagonist magnesium sulfate (MgSO4). We hypothesized that MgSO4 therapy would improve outcomes in ferrets with hydrocephalus induced with kaolin at 15 days. METHODS: MRI was performed at 29 days to assess ventricle size and stratify ferrets to treatment conditions. Beginning at 31 days age, they were treated daily for 14 days with MgSO4 (9 mM/kg/day) or sham saline therapy, and then imaged again before sacrifice. Behavior was examined thrice weekly. Histological and biochemical ELISA and myelin enzyme activity assays were performed at 46 days age. RESULTS: Hydrocephalic ferrets exhibited some differences in weight and behavior between treatment groups. Those receiving MgSO4 weighed less, were more lethargic, and displayed reduced activity compared to those receiving saline injections. Hydrocephalic ferrets developed ventriculomegaly, which was not modified by MgSO4 treatment. Histological examination showed destruction of periventricular white matter. Glial fibrillary acidic protein content, myelin basic protein content, and myelin enzyme activity did not differ significantly between treatment groups. CONCLUSION: The hydrocephalus-associated disturbances in juvenile ferret brains are not ameliorated by MgSO4 treatment, and lethargy is a significant side effect.

Hydrocephalus induced via intraventricular kaolin injection in adult rats.

Hydrocephalus is a common neurological disease in humans, but a uniform and particularly effective hydrocephalic animal model amenable to proper appraisal and deep study has not yet been established. In this study, we attempted to construct a high-efficiency model of hydrocephalus via intraventricular kaolin injection. Adult male Sprague-Dawley rats were randomly divided into 2 groups: the control group (n = 15) and the experimental group (n = 30). Kaolin was injected into the lateral ventricle of experimental animals. Control rats underwent the same procedure but received sterile saline injection instead of kaolin. All animals with kaolin injection into the lateral ventricle developed hydrocephalus according to magnetic resonance imaging (MRI) results (success rate up to 100%). Also, the Morris water maze (MWM) test demonstrated disturbed spatial learning and memory. Furthermore, there were significant differences between groups with respect to the histological changes in the periventricular tissue. Our results indicate that experimental hydrocephalus induced by lateral ventricle injection of kaolin in adult rats is feasible and may be widely used.

Biodegradability and swelling capacity of kaolin based chitosan-g-PHEMA nanocomposite hydrogel.

Chitosan, a natural biopolymer, obtained by alkaline deacetylation of chitin, exhibits excellent biological properties such as biodegradability, immunological and antibacterial activity. Recently, there has been a growing interest in the chemical modification of chitosan in order to widen its applications. The chemical modification of chitosan has been achieved via grafting of monomer, 2-hydroxyethyl methacrylate (HEMA) in the presence of the initiator, ammonium persulfate (APS) and kaolin was added to improve the mechanical strength of the newly developed nanocomposites hydrogel. The so prepared grafted nanocomposites hydrogel was characterized by FTIR, XRD, SEM, TEM and TGA. The equilibrium water content (EWC) of the samples were measured at different pH ranges 6.5-8.0 and found optimum at pH 7.5 for biomedical applications. Further, the biodegradability of the samples was studied at different time intervals from 15 days to 1 year but, the kaolin based nanohydrogels exhibited good biodegradability.