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Non-invasive detection of ketosis and its application in refractory epilepsy.

Ketosis is believed to be necessary to the anticonvulsant mechanism of the ketogenic diet; however, the relationship between ketosis and seizure control has not been established. The various analytical methods for the assessment of ketosis are reviewed, and their application in the area of epilepsy and the ketogenic diet is evaluated. The clinical challenges inherent in interpreting measures of ketosis are discussed, as are suggestions for future studies.

Acetone↗

Expression of alpha-7 nAChRs on spinal cord-brainstem neurons controlling inspiratory drive to the diaphragm.

In the present study, we determined whether alpha-7 subunit containing nicotinic acetylcholine receptors (nAChRs) are expressed by neurons within the pre-Botzinger complex (pre-BotC), bulbospinal, and phrenic motor nuclei in the rat. alpha-7 Immunohistochemistry combined with cholera toxin B (CTB), a retrograde tracer was used to detect expression of alpha-7 nAChRs by phrenic motor and bulbospinal neurons. Neurokinin-1 receptor immunoreactivity was used as a marker for pre-BotC neurons. Of the CTB-positive neurons in the phrenic nuclei, 60% exhibited immunoreactivity for alpha-7 nAChRs. Of the bulbospinal neurons in the paramedian reticular nuclei (PMn), gigantocellular nuclei (Gi), raphe nuclei, rostral ventrolateral medulla (RVLM) and nucleus tractus solitarius, 20-50% were found to express alpha-7 nAChR immunoreactivity. Of the peudorabies virus (PRV) labeled bulbospinal neurons in PMn, Gi, raphe and RVLM, 9-12% co-expressed alpha-7 nAChRs. Immunoreactivity for alpha-7 nAChRs was also detected in 57% of the neurokinin-1 receptor containing neurons presumed to reside in pre-BotC. These findings suggest that nicotinic cholinergic regulation of the chest wall pumping muscles may occur at multiple levels of the central nervous system.

Animals↗

Adenosine A2A receptors interact with GABAergic pathways to modulate respiration in neonatal piglets.

GABA and adenosine contribute to respiratory inhibition in early postnatal life. In this study the adenosine A2A receptor agonist CGS21680 was used to evaluate adenosine receptor specificity and the interrelation of adenosine and GABA in the inhibition of inspiratory drive. In neonatal piglets (n = 10), CGS21680 was injected into the fourth ventricle resulting in apnea and/or decreased burst area and frequency of phrenic discharge. Phrenic burst area decreased to 58.9 +/- 8.6% (S.E.M.) after CGS21680 injection (control = 91.8 +/- 1.0%). Expiratory time increased 261.0 +/- 59.9% after CGS21680 from control (87.7 +/- 2.7%). When bicuculline was injected locally within the rostral ventrolateral medulla (n = 5), or into the fourth ventricle (n = 5), the CGS21680 induced inhibition of phrenic was abolished. To define expression of A2A receptor at the message level (mRNA), we employed in situ hybridization with a digoxigenin-coupled oligonucleotide. Adenosine A2A receptor mRNA was expressed in regions of the medulla oblongata known to contain GABAergic neurons. We conclude that GABAergic inputs affecting respiratory timing and inspiratory drive are modulated by activation of A2A receptors. These findings offer new insight into the mechanism whereby xanthine therapy diminishes apnea of prematurity.

Adenosine↗

Hypercapnic and hypoxic responses require intact neural transmission from the pre-Bötzinger complex.

The central respiratory network that includes the pre-Bötzinger complex (pre-BötC), a region believed to contain rhythmogenic neurons, is capable of responding to fluctuations in CO2 and pH. However, the role of inputs from this site in mediating ventilatory responses to hypercapnia and/or hypoxia in nonsedated animals is not well established. Therefore, in the present study we tested the hypothesis that altered transmission from the pre-BötC to its target sites would decrease chemosensory responsiveness to acute hypercapnia and modulate the ventilatory response to hypoxia. Colchicine was used to block axonal transport. At 48 h after bilateral microinjections of colchicine into the pre-BötC (100 microg/uL, 100 nL/site), but not saline, the baseline frequency of breathing decreased; however, rhythmicity was not altered. In addition, there was a significant fall in the ventilatory response to hypercapnia (5 and 12% CO2) and hypoxia (8% O2). These findings indicate that, inputs from pre-BötC neurons are of critical importance in providing the normal ventilatory response to both hypercapnia and hypoxia.

Analysis of Variance↗

An astrocyte toxin influences the pattern of breathing and the ventilatory response to hypercapnia in neonatal rats.

Recent in vitro data suggest that astrocytes may modulate respiration. To examine this question in vivo, we treated 5-day-old rat pups with methionine sulfoximine (MS), a compound that alters carbohydrate and glutamate metabolism in astrocytes, but not neurons. MS-treated pups displayed a reduced breathing frequency (f) in baseline conditions relative to saline-treated pups. Hypercapnia (5% CO(2)) increased f in both groups, but f still remained significantly lower in the MS-treated group. No differences between treatment groups in the responses to hypoxia (8% O(2)) were observed. Also, MS-treated rats showed an enhanced accumulation of glycogen in neurons of the facial nucleus, the nucleus ambiguus, and the hypoglossal nucleus, structures that regulate respiratory activity and airway patency. An altered transfer of nutrient molecules from astrocytes to neurons may underlie these effects of MS, although direct effects of MS upon neurons or upon peripheral structures that regulate respiration cannot be completely ruled out as an explanation.

Animals↗

Ablation of vagal preganglionic neurons innervating the extra-thoracic trachea affects ventilatory responses to hypercapnia and hypoxia.

This study tested the hypothesis that during hypercapnia or hypoxia, airway-related vagal preganglionic neurons (AVPNs) of the nucleus ambiguus (NA) release acetylcholine (ACh), which in a paracrine fashion, activates ACh receptors expressed by inspiratory rhythm generating cells. AVPNs in the NA were ablated by injecting a saporin- (SA) cholera toxin b subunit (CTb-SA) conjugate into the extra-thoracic trachea (n=6). Control animals were injected with free CTb (n=6). In CTb treated rats, baseline ventilation and ventilatory responses to hypercapnia (5 and 12% CO(2) in O(2)) or hypoxia (8% O(2) in N(2)) were similar (p>0.05) prior to and 5 days after injection. CTb-SA injected rats maintained rhythmic breathing patterns 5 days post injection, however, tachypneic responses to hypercapnia or hypoxia were significantly reduced. The number of choline acetyltransferase (ChAT) immunoreactive cells in the NA was much lower (p<0.05) in CTb-SA rats as compared to animals receiving CTb only. These results suggest that AVPNs participate in the respiratory frequency response to hypercapnia or hypoxia.

Animals↗

CNS determinants of sleep-related worsening of airway functions: implications for nocturnal asthma.

This review summarizes the recent neuroanatomical and physiological studies that form the neural basis for the state-dependent changes in airway resistance. Here, we review only the interactions between the brain regions generating quiet (non-rapid eye movement, NREM) and active (rapid eye movement, REM) sleep stages and CNS pathways controlling cholinergic outflow to the airways. During NREM and REM sleep, bronchoconstrictive responses are heightened and conductivity of the airways is lower as compared to the waking state. The decrease in conductivity of the lower airways parallels the sleep-induced decline in the discharge of brainstem monoaminergic cell groups and GABAergic neurons of the ventrolateral periaqueductal midbrain region, all of which provide inhibitory inputs to airway-related vagal preganglionic neurons (AVPNs). Withdrawal of central inhibitory influences to AVPNs results in a shift from inhibitory to excitatory transmission that leads to an increase in airway responsiveness, cholinergic outflow to the lower airways and consequently, bronchoconstriction. In healthy subjects, these changes are clinically unnoticed. However, in patients with bronchial asthma, sleep-related alterations in lung functions are troublesome, causing intensified bronchopulmonary symptoms (nocturnal asthma), frequent arousals, decreased quality of life, and increased mortality. Unquestionably, the studies revealing neural mechanisms that underlie sleep-related alterations of airway function will provide new directions in the treatment and prevention of sleep-induced worsening of airway diseases.

Airway Resistance↗

Phenotypic traits of the hypothalamic PVN cells innervating airway-related vagal preganglionic neurons.

The paraventricular nucleus of the hypothalamus (PVN) integrates multiple inputs via projections from arginine vasopressin (AVP)- and oxytocin (OXT)-containing neurons to the brain stem and spinal cord as well as regulates respiratory and cardiovascular stress-related responses, which also affect airway function. In the present study, we used immunocytochemistry and the retrograde transneuronal tracer, Bartha strain of pseudorabies virus expressing green fluorescent protein (PRV-GFP), to localize AVP- and OXT-producing neurons that project to airway-related vagal preganglionic neurons (AVPNs) innervating intrapulmonary airways. PRV-GFP was microinjected into the upper right lung lobe, and after 4 days survival, hypothalamic tissue sections were processed for co-expression of PRV-GFP and AVP or PRV-GFP and OXT. In addition, in a separate group of five rats, Phaseolus vulgaris leucoagglutinin (PHAL), an anterograde tracer, was injected unilaterally into the PVN and cholera toxin beta subunit was microinjected into the tracheal wall. Analysis of five successfully infected animals showed that 14% of PRV-GFP labeled neurons express AVP traits and 18% of transneuronally-labeled neurons contain OXT. Furthermore, the identified AVPNs innervating extrathoracic trachea receive axon terminals of the PVN neurons. The results indicate that AVP- and OXT-producing PVN cells, via direct projections to the AVPNs, could modulate cholinergic outflow to the airways, as a part of overall changes in response to stress.

Animals↗

Synthesis characterization and biological study of diorganotin(IV) complexes of monomethyl phthalate.

The synthesis and characterization of new coordination compounds of some organotin(IV) chlorides with monomethyl phthalate is reported; the ligand molecules appear to be bound to the tin atom through carbonyl oxygen atoms. Their structures have been characterized by elemental analyses, molar conductance, and bonding in these complexes is discussed in terms of their IR, (1)H, (13)C, (119)Sn NMR and (119 m)Sn Mössbauer spectral studies. The spectroscopic results obtained are in full agreement with the proposed 2:1 stoichiometry. The complexes soluble in DMSO have been screened against a wide spectrum of bacteria and the results obtained are quite promising. The LD(50) values have also been determined in the albino rats. Some of the complexes also exhibit high anti-inflammatory activity.

Animals↗

Optical fibre chemical sensor for trace vanadium(V) determination based on newly synthesized palm based fatty hydroxamic acid immobilized in polyvinyl chloride membrane.

Fatty hydroxamic acid (FHA) immobilized in polyvinyl chloride (PVC) has been studied as a sensor element of an optical fibre chemical sensor for V(V). By using this instrument, V(V) in solution has been determined in the log concentration range of 0-2.5 (i.e. 1.0-300 mg/L). The detection limit was 1.0 mg/L. The relative standard deviation (R.S.D.) of the method for the reproducibility study at V(V) concentration of 200 mg/L and 300 mg/L were calculated to be 2.9% and 2.0%, respectively. Interference from foreign ions was also studied at 1:1 mole ratio of V(V):foreign ions. It was found that, Fe(III) ion interfered most in the determination of vanadium(V). Excellent agreement with ICP-AES method was achieved when the proposed method was applied towards determination of V(V).

Arecaceae↗

Impacts of mercury contaminated mining waste on soil quality, crops, bivalves, and fish in the Naboc River area, Mindanao, Philippines.

Rice paddy fields in the Naboc area, near Monkayo on the island of Mindanao, Philippines, have been irrigated four times a year over the last decade using Naboc River water contaminated with mercury (Hg) by artisanal gold mining in the Diwalwal area. Silt containing up to at least 90 mg Hg/kg (d.w.) has been deposited in rice paddy fields during the 1990s and this has been repeatedly mixed into the rice root zone through ploughing. Hg in the rice paddy field soils averages 24 mg Hg/kg and generally exceeds the UK and Canadian soil quality thresholds for agricultural soils as well as the proposed Dutch Intervention value and the USEPA soil ingestion Soil Screening Level (SSL) for inorganic Hg. Much lower Hg concentrations (0.05-0.99 mg/kg) within the range expected for uncontaminated soils, characterise soils on which corn and bananas are cultivated, largely because these are not irrigated with Hg-contaminated water from the Naboc River. The estimated total weekly MeHg intake for a person living in the Naboc area related to the weekly consumption of 2.1 kg of rice grown on Hg-contaminated soils (15 microg MeHg) in conjunction with 1 kg of fish (220 microg MeHg) and 100 g of mussels (50 microg MeHg) from the Naboc River, would total 285 microg MeHg (equivalent to 4.75 microg/kg bw for a 60 kg adult), which is nearly three times the JECFA PTWI of 1.6 microg/kg bw. This will significantly contribute to the population mercury exposure and might explain why 38% of the local inhabitants were classified as Hg intoxicated during a mercury toxicity assessment [Drasch GS, Böse, O'Reilly S, Beinhoff C, Roider G, Maydl S. The Mt. Diwata study on the Philippines 1999-assessing mercury intoxication of the population by small scale gold mining. Sci Total Environ 2001; 267(1-3): 151-168.].

Animals↗

Water quality and macroinvertebrate community response following pesticide applications in a banana plantation, Limon, Costa Rica.

Pesticides used in banana production may enter watercourses and pose ecological risks for aquatic ecosystems. The occurrence and effects of pesticides in a stream draining a banana plantation was evaluated using chemical characterization, toxicity testing and macrobenthic community composition. All nematicides studied were detected in the surface waters of the banana plantation during application periods, with peak concentrations following applications. Toxicity tests were limited to the carbofuran application and no toxicity was observed with the acute tests used. However, since pesticide concentrations were generally below the lowest LC50 value for crustaceans but above calculated aquatic quality criteria, there remains a risk of chronic toxicity. Accurate ecological assessments of pesticide use in banana plantations are currently limited by the lack of local short-term chronic toxicity tests and tests using sensitive native species. Relatively constant levels of four pesticides (imazalil, thiabendazole, chlorpyrifos and propiconazole), which had toxic effects according to the 96h hydra and 21d daphnia chronic test, were recorded in the effluent of the packing plant throughout the study, indicating that the solid waste trap used in this facility was not effective in eliminating toxic chemicals. Certain taxa, such as Heterelmis sp. (Elmidae), Heteragrion sp. (Megapodagrionidae, Odonata), Caenis sp. (Caenidae, Ephemerotera), and Smicridea sp. (Hidropsychidae, Trichoptera), were more abundant at reference sites than in the banana farm waters, and may be good candidates for toxicity testing. Multivariate analyses of the macroinvertebrate communities clearly showed that the banana plantation sites were significantly different from the reference sites. Moreover, following the pesticide applications, all the banana plantation sites showed significant changes in community composition, with the same genera being affected at all sites and for all pesticides (terbufos, cadusafos and carbofuran). Consequently, the results presented here show that multivariate analysis of community composition was more sensitive in distinguishing pesticide effects than the toxicity tests and richness and composition measures used. We conclude that monitoring macroinvertebrate communities can be a powerful tool in the assessment of ecological effects of banana production.

Agriculture↗

Sagliker syndrome: uglifying human face appearance in late and severe secondary hyperparathyroidism in chronic renal failure.

Almost every patient with chronic renal failure (CRF) eventually develops secondary hyperparathyroidism (SH) unless they are treated with proper and novel medications in advanced medical centers by skilled medical personnel. Every kind of bone abnormality including skull deformities has been described in detail by almost every concerned researcher and textbook, but descriptions of this phenomenon are limited in the medical literature to the years from 1973 to 1977. To our knowledge, extensive data regarding uglifying human face appearances have not been defined so far in the literature. We are therefore making this addition to the clinical nephrology field by accumulating such data. After we found 2 consecutive peculiar and unique patients with uglifying human face appearances in 2000, we attempted to inform and draw attention to this new entity to all hemodialysis (HD) centers in Turkey, as well as in other developing countries around the world to collect data on this phenomenon. Accordingly, we visited dialysis centers and patients' houses to collect detailed information, including medical clinical histories, physical examinations, laboratory data, biographies, current medications, and so forth. We found 25 patients who had CRF, SH, short stature, extremely severe skull changes, maxillary and mandibular bone changes, teeth/dental abnormalities, and soft and innocuous tumoral tissues in the mouth (hence, uglifying the appearance of the face), fingertip changes, severe psychologic problems, and depression. It appears that patients with CRF may have a new syndrome of bone deformities that have long been neglected, ignored, and forgotten since the mid-1970s when they were first described. This is vital and critical information for the clinical status of patients who suffered from the syndrome that we have named Sagliker syndrome (SS), and we believe there are many more patients in the world who are suffering from it.

Abnormalities, Multiple↗

Investigation of destruxin A and B from 80 Metarhizium strains in China, and the optimization of cultural conditions for the strain MaQ10.

The production levels of destruxin A and B (DA and DB) of 80 Metarhizium strains from China were investigated. The average yields of DA and DB were 14.87+/-2.30 and 3.65+/-0.58 microg/mL, respectively. The strains isolated from soil had significantly (p<0.05) lower production of DA and DB than the strains isolated from insect cadavers. Also, there was a positive correlation in the yields of DA and DB, and the regressive equations were established. Of the 80 strains, MaQ10 had the highest yields of DA and DB, amounted to 106.78+/-9.41 and 29.52+/-2.63 microg/mL, respectively, at 10 days fermentation period. Followed by the strains MaQ05, MaQ07 and MaQ12, their yields of DA were 79.72+/-5.36, 77.69+/-8.54 and 70.04+/-10.1 microg/mL, respectively, and DB were 16.81+/-1.51, 13.38+/-0.41 and 16.88+/-1.15 microg/mL, respectively. Furthermore, the cultural conditions of MaQ10 were optimized to produce DA and DB. The optimal inoculum, initial pH, temperature and rotary speed were 8%, pH 9.0, 27 degrees C and 240 r/min for DA, and 8%, pH 9.0, 25 degrees C and 220 r/min for DB. Under these optimal culture conditions, the predicted production of DA and DB was 193.87 and 39.85 microg/mL, and the actual production was 189.13 and 43.35 microg/mL, respectively.

Animals↗

Severe angioedema caused by banana allergy under tacrolimus immunosuppression.

Occurrences of allergic reactions induced by various foods have been reported in pediatric liver graft recipients receiving tacrolimus immunosuppression. We describe herein a female infant, who was admitted to our hospital with life-threatening angioedema because of banana hypersensitivity, 8 months after orthotopic liver transplantation. Food allergies should be screened in all tacrolimus-immunosuppressed pediatric liver recipients who show suggestive clinical symptoms. Banana must be added to allergen batteries during etiologic investigations. Cyclosporine represents an option for drug conversion to prevent organ rejection.

Biliary Atresia↗

Multiple suppurative cystic lesions of the lips and buccal mucosa: a case of suppurative stomatitis glandularis.

Cheilitis glandularis (CG) is a rare inflammatory salivary gland disease that usually affects the lips. Although the etiology of CG is still unknown, it is believed to be a hereditary disease with an autosomal dominant pattern of inheritance. Three clinical presentations of CG are described in the literature: simple, superficial suppurative, and deep suppurative. A case of deep suppurative CG that extended to the buccal mucosa has been previously reported as suppurative stomatitis glandularis (SSG). Here we report a case of SSG in a 64-year-old white female with a history of bilateral renal transplants for adult polycystic kidney disease, who presented with painful swollen lips and bilateral buccal mucosal lesions. The diagnosis and management of the case is discussed. To the best of our knowledge, this is the second report of SSG, a rare condition affecting the minor salivary glands in the oral cavity.

Cheilitis↗

Uncommon clinical presentations of cutaneous leishmaniasis in Sudan.

Cutaneous leishmaniasis in Sudan is caused by Leishmania major zymodeme LON1. Self-healing usually occurs within 1 year but occasionally its duration is prolonged and treatment is required. The clinical forms are ulcers, nodules and noduloulcerative lesions. Here we describe seven patients with uncommon lesions that were difficult to recognize as Leishmania infections. These included mycetoma-like lesions, lesions that resembled L. tropica infection and others. One HIV/AIDS patient had Kaposi's sarcoma with Leishmania parasites in the Kaposi lesions. Most of these uncommon clinical forms were difficult to treat. The diagnosis depended on a high degree of suspicion and the demonstration of parasites in smears or culture. PCR was used to characterize parasites from the patients described here. Leishmania major was found by kDNA PCR in all patients, except one, who had a leishmanioma due to L. donovani. In three patients, including one with a L. tropica like-lesion, the parasites were confirmed as L. major by gp63 PCR-RFLP.

Adult↗