Ch Administration Research Articles

Edible wild plants, chicory and purslane, alleviated diabetic testicular dysfunction, and insulin resistance via suppression 8OHdg and oxidative stress in rats.

Testicular dysfunction is a prevalent health problem frequently reported in individuals with diabetes mellitus (DM). Oxidative-inflammatory reactions, hormonal and spermatic abnormalities often accompany this illness. Herbal remedies "particularly wild plants" including chicory (Chicorium Intybus) and purslane (Portulaca Oleracea) are emerging as popular agents for people dealing with these issues due to their ability to act as antioxidants, reduce inflammation, and exhibit antidiabetic effects. According to the collected data, the daily administration of chicory (Ch) seed-extract (250 mg/kg) or purslane (Pu) seed-extract (200 mg/kg) to streptozotocin (STZ)-induced diabetic rats (50 mg/kg) for 30 days resulted in the normalization of fasting blood glucose (FBG), serum fructosamine, insulin levels, and insulin resistance (HOMA-IR), as well as reducing lipid peroxidation end-product malondialdehyde (MDA) level, aldehyde oxidase (AO) and xanthene oxidase (XO) activities. While caused a considerable improvement in glutathione (GSH) content, superoxide dismutase (SOD), catalase (CAT) activity, and total antioxidant capacity (TAC) when compared to diabetic rats. Ch and Pu extracts had a substantial impact on testicular parameters including sperm characterization, testosterone level, vimentin expression along with improvements in body and testis weight. They also mitigated hyperlipidemia by reducing total lipids (TL), total cholesterol (TC) levels, and low-density lipoprotein cholesterol (LDL-C), while increasing high-density lipoprotein cholesterol (HDL-C). Furthermore, oral administration of either Ch or Pu notably attuned the elevated proinflammatory cytokines as tumor necrotic factor (TNF-α), C-reactive protein (CRP), and Interleukin-6 (IL-6) together with reducing apoptosis and DNA damage. This was achieved through the suppression of DNA-fragmentation marker 8OHdG, triggering of caspase-3 immuno-expression, and elevation of Bcl-2 protein. The histological studies provided evidence supporting the preventive effects of Ch and Pu against DM-induced testicular dysfunction. In conclusion, Ch and Pu seed-extracts mitigate testicular impairment during DM due to their antihyperglycemic, antilipidemic, antioxidant, anti-inflammatory, and antiapoptotic properties.

Protective Effects of Chrysin on Hippocampal Damage Induced by Chlorpyrifos in Adult Rats.

This study aimed to evaluate the possible effects of chlorpyrifos on the rat hippocampus and evaluate whether these effects can be decreased with chrysin co-administration in an animal model. Male Wistar rats were randomly divided into 5 groups; Control (C), Chlorpyrifos (CPF), Chlorpyrifos + Chrysin (12.5 mg/kg) (CPF + CH1), Chlorpyrifos + Chrysin (25 mg/kg) (CPF + CH2), Chlorpyrifos + Chrysin (50 mg/kg) (CPF + CH3). After 45 days, hippocampus tissues were evaluated by biochemical and histopathological tests. Biochemical findings indicated that CPF and CPF plus CH administration could not significantly change SOD activity, and MAD, GSH, and NO levels in the hippocampus tissue of animals versus controls. Histopathological findings of the toxic effects of CPF on hippocampus tissue as evidenced by inflammatory cell infiltration, degeneration/necrosis, and mild hyperemia. CH could ameliorate these histopathological changes in a dose-dependent manner. In conclusion, CH was effective against histopathological damage induced by CPF in the hippocampus through modulating inflammation and apoptosis.

Choline chloride modulates learning, memory, and synaptic plasticity impairments in maternally separated adolescent male rats.

Maternal separation (MS) is a model to induce permanent alternations in the central nervous system (CNS) and is associated with increased levels of anxiety and cognitive deficiencies. Since methyl donor choline (Ch) has been shown to play a significant role in learning and memory and enhance synaptic plasticity, the authors hypothesized that Ch may attenuate MS-induced impairments in synaptic plasticity and cognitive performance. Rat pups underwent an MS protocol for 180 min/day from postnatal day (PND) 1 to 21. Ch was administered subcutaneously (100 mg/kg, 21 days) to the choline chloride and MS +choline chloride groups from PND 29 to 49. Anxiety-like behaviour, recognition memory, and spatial and passive avoidance learning and memory were measured in the adolescent rats. In addition, evoked field excitatory postsynaptic potentials (fEPSP) were recorded from the CA1 region of the hippocampus. MS induced higher anxiety-like behaviour in the animals. It also impaired learning and memory. However, MS had no effect on locomotor activity. Subcutaneous administration of Ch attenuated MS-induced cognitive deficits and enhanced the learning and memory of MS rats. Ch also decreased anxiety-like behaviour in the open-field test. The present results showed that long-term potentiation (LTP) was induced in all groups except MS and MS + saline animals. However, Ch injection induced LTP and had maintenance in MS + choline chloride, but it was not statistically significant compared with the MS group. In summary, the present findings indicate that MS can interfere with normal animal's cognition and subcutaneous of Ch may be considered an appropriate therapeutic strategy for promoting cognitive dysfunctions in MS animals.

Crassifoside H improve the depressive-like behavior of rats under chronic unpredictable mild stress: Possible involved mechanisms.

Crassifoside (CH) is a novel chlorine-containing compound isolated from rhizomes of Curculigo glabrescens. This study aimed to explore the antidepressant-like effect of CH and involved mechanisms. A rat depression model was established using chronic unpredictable mild stress (CUMS) paradigm. Behavioral tests including sucrose preference test (SPT), open field test (OFT) and forced swimming test (FST) were used to evaluate the antidepressant-like effect of CH. The levels of plasma corticosterone (CORT) and corticotrophin-releasing factor (CRF) in hypothalamus were measured to determine the activity of hypothalamic pituitary-adrenal (HPA) axis. Protein expression of 5-hydroxytryptamine 1A (5-HT1A) receptor, brain-derived neurotrophic factor (BDNF), as well as the total and phosphorylated extracellular signal-regulated kinase (ERK)1/2 in hippocampus were also analyzed by Western blotting. The CH administration effectively ameliorated the depressive-like behaviors of CUMS rats, as indicated by the increased sucrose intake in SPT, reduced immobility time in FST, and the increased rearing and grooming numbers, spent more time in inner zone and less time in outer zone in OFT. CH improved CUMS-induced HPA axis hyperactivity by reduced plasma CORT and CRH expression in hypothalamus. Moreover, CH reversed CUMS-induced decrease of 5-HT1A receptor expression, and up-regulated BDNF and phosphorylated-ERK1/2 levels in hippocampus. These findings suggest that CH improved depressive behaviors of CUMS rats by modulating of HPA axis dysfunction, increasing 5-HT1A receptor expression, and activating BDNF-ERK signaling pathway.

Protective effect of gelatin polypeptides from Pacific cod (Gadus macrocephalus) against UV irradiation-induced damages by inhibiting inflammation and improving transforming growth factor-β/Smad signaling pathway

Exposure to ultraviolet (UV) radiation results in skin damage, collagen reduction in the dermis, and consequently, premature skin aging (photoaging). The goal of this study was to examine the effect of gelatin hydrolysate (CH) from pacific cod (Gadus macrocephalus) skin on UV irradiation-induced inflammation and collagen reduction of photoaging mouse skin. The effect of CH on the activities of endogenous antioxidant enzymes was investigated. The expressions of nuclear factor-κB (NF-κB), proinflammatory cytokines, type I and type III procollagen, transforming growth factor-β1 (TGF-β1), type II receptor of TGF-β1 (TGF-βRII), and Smad7 were determined using quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) and ELISA. The results showed that oral administration of CH suppressed UV irradiation-induced damages to skin by inhibiting the depletion of endogenous antioxidant enzyme activity, and by suppressing the expression of NF-κB as well as NF-κB-mediated proinflammatory cytokines expression. Furthermore, CH inhibited type I procollagen synthesis reduction by up-regulating TβRII level and down-regulating Smad7 level, which demonstrates that CH is involved in matrix collagen synthesis by activating the TGF-β/Smad pathway in the photoaging skin. Based on these results, we conclude that CH protected skin from UV irradiation-induced photodamages, and CH may be a potentially effective agent for the prevention of photoaging.

Phosphorus 30 CH to control Varroa population in Apis mellifera colonies

IntroductionVarroa destructor is considered to be the main cause of European honeybee (Apis mellifera ssp. Linnaeus 1758) colony losses. The use of homeopathic products in veterinary practices has consistently increased in the last 50 years, but limited data are available on the application of homeopathic treatments to honeybees.The aims of this study were to investigate the acaricide efficacy and tolerability for honeybees treated for 35days with the homeopathic product Phosphorus 30 CH. MethodsThe clinical trial was carried out during the summer of 2012 in Central Italy. Twenty-four honeybee colonies were evenly divided into two different groups: one treated with Phosphorus 30 CH (12 colonies) and one left untreated (12 colonies). The mite mortality rate of the remedy was evaluated by counting the number of fallen mites on the sticky boards placed on the bottom tray of the hives every 3days. Oxalic acid administration in an absence of brood was used to estimate the number of surviving mites. To assess the honeybee tolerability to the treatment, immediately before and after the Phosphorus 30 CH administration, an evaluation of the adult honeybee population was performed. ResultsThe results revealed that no efficacy differences (p-value=0.079, U=23; EV=45; Variance (U)=150), nor differences in hive strengths (p-value=0.118; U=25.5; EV=45; Variance (U)=147.76) were observed in the treated group compared to the untreated group. ConclusionOur results are consistent with other studies conducted using homeopathic remedies to control varroa mites in Apis mellifera colonies. Further studies are needed to compare our data with different treatment durations, different administration methods and potency of the remedy.

Enhanced bioavailability of nano-sized chitosan–atorvastatin conjugate after oral administration to rats

A novel approach to improve the bioavailability and stability of atorvastatin (AT) was developed by constructing a nano-sized polymer–atorvastatin conjugate. Firstly, a novel chitosan–atorvastatin (CH–AT) conjugate was efficiently synthesized through amide coupling reaction. The formation of conjugate was confirmed by 1H NMR and FT-IR spectrometry. Nano-sized conjugate with a mean size of 215.3 ± 14.2 nm was prepared by the process of high pressure homogenization (HPH). Scanning electron microscopy (SEM) revealed that CH–AT nano-conjugate possess smooth surface whereas X-ray diffraction (XRD) spectra demonstrated amorphous nature of nano-conjugate. Further, CH–AT nano-conjugate showed solubility enhancement of nearly 4-fold and 100-fold compared to CH–AT conjugate and pure AT, respectively. In vitro drug release studies in simulated gastric fluid and simulated intestinal fluid suggested sustained release of AT from the conjugate. Additionally, the nano-conjugate significantly reduced the acidic degradation of AT. The plasma-concentration time profile of AT after oral administration of CH–AT nano-conjugate (2574 ± 95.4 ng/mL) to rat exhibited nearly 5-fold increase in bioavailability compared with AT suspension (583 ± 55.5 ng/mL). Finally, variable bioavailability, as observed for AT suspension was also reduced when AT was administered in form of CH–AT nano-conjugate. Taken together these data demonstrate that chitosan conjugate nano-prodrugs may be used as sustained polymeric prodrugs for enhancing bioavailability.

Ondansetron (O) with or without dexamethasone (D) for the prevention of chemotherapy (C)-induced nausea and vomiting (CINV)

18558 Background: Adition of D to the standard antiemetic treatment for CINV prevention is frequent, despite the lack of benefit evidence in controlled clinical trials. In this study we compare the impact of O treatment with or without D on daily life, in patients (pts) under treatment with high or moderately emetogenic C. Methods: Longitudinal, randomized and prospective study. All pts who received anticancer treatment with high or moderately emetogenic C were included, and randomly assigned to group A (O 8 mg iv and D 8 mg iv) or group B (O 8 mg iv). Evaluable pts did not have to receive any medication which could modify the antiemetic effect of treatment within the 24 hours following the administration of CH and had to be able to answer an autoadministered questionnaire. After 24 hours, the Functional Living Index- Emesis (FLIE), a daily life index which consists of 18 questions divided into two domains: nausea and vomiting, had to be completed. Data were analyzed by independent mean sample t-test, and ANOVA One-Way, with a 0.05 significance level. Results: Between December/04 and November/05 233 patients (age average: 59.24; range 21–87) were randomly assigned to antiemetic treatment with (n = 125) or without D (n = 108). Both groups were well balanced as regards the type of chemotherapy, sex and age, and all patients were evaluable. No significant effects were observed between both groups when the global data were analyzed. However, when the sample was stratified by type of chemotherapy, a significantly lower impairment (55.1 vs 51.3; p < .05) was detected in the nausea domain in those patients who received moderately emetogenic chemotherapy. Conclusion: In our sample of patients we observed benefits in the impact on daily life, by the addition of D to the O as preventive treatment of CINV, in those patients that received moderately emetogenic chemotherapy. No significant financial relationships to disclose.

A tryptic hydrolysate from bovine milk α S1-casein improves sleep in rats subjected to chronic mild stress

The putative effects of a tryptic bovine α S1-casein hydrolysate on stress-induced sleep disorders were investigated and their possible link with typical blood stress parameters such as plasma corticosterone concentrations and glycaemia was assessed. Rats were subjected to chronic stress in the form of environmental disturbances, while receiving an oral administration of the α S1-casein hydrolysate (CH). Chronic stress significantly reduced sleep duration in control rats during the first 2 days of the stress period, but stress-induced sleep disturbance was prevented in CH-treated rats. Indeed, CH administration allowed the maintenance of slow wave sleep (SWS) duration and even a slight increase in paradoxical sleep (PS) duration in treated rats. Results on plasma corticosterone concentrations and on glycemia values were inconclusive with respect to the implication of the HPA axis in this study. However, the protective effect of the α S1-casein hydrolysate on sleep during exposure to our chronic mild stress conditions may be mediated by modulation of the central adrenergic response.

Therapeutic administration of 3,4,5-trimethoxy-4'-fluorochalcone, a selective inhibitor of iNOS expression, attenuates the development of adjuvant-induced arthritis in rats.

We have previously investigated the effects of a series of dimethoxy- and trimethoxychalcone derivatives, with various patterns of fluorination, on nitric oxide production in LPS-stimulated murine RAW 264.7. The present study was designed to determine if 3,4,5-trimethoxy-4'-fluorochalcone (CH 17) could modulate the production of NO and/or prostaglandins in vivo. On the mouse macrophage cell line RAW 264.7 CH 17 inhibited dose-dependently NO production, with an IC(50) value in the nanomolar range, and reduced PGE(2) levels by a 58% at 10 microM. This compound had no direct inhibitory effect on iNOS and COX-2 activities. NO reduction was the consequence of inhibition of the expression of iNOS. In vitro experiments indicated that CH 17 is an inhibitor of the nuclear factor-kappaB (NF-kappaB) pathway of cellular activation in macrophages. This compound exhibited in vivo an inhibitory behaviour correlated with its in vitro results on nitrite and PGE(2) accumulation. In the rat adjuvant-induced arthritis, oral administration of CH 17 (25 mg/kg) on days 17-24 after adjuvant injection, significantly inhibited paw oedema, protected from weight loss and reduced the levels of inflammatory mediators (nitrites and PGE(2)) in paw homogenates, without affecting PGE(2) levels in stomach homogenates. The profile and potency of this compound, a selective inhibitor of iNOS expression that interferes with NF-kappaB activation, may have relevance for the inhibition of the inflammatory response, representing a new approach to the modulation of different inflammatory pathologies.

Enhanced antitumor activity of a combination treatment with a mouse/human chimeric anti-MK-1 antibody and lymphokine-activated killer cells in vitro and in a severe combined immunodeficient mouse xenograft model.

Mouse monoclonal antibody FU-MK-1, raised against a human gastric adenocarcinoma, recognizes a glycoprotein antigen (termed MK-1 antigen) present on most carcinomas and seems to be valuable in immunodiagnosis and immunotherapy of various cancers. In a recent study, we constructed a mouse/human chimeric antibody, designated Ch FU-MK-1, by fusing the FU-MK-1 V(H) and Vkappa genes to the human Cgamma1 and Ckappa genes, respectively. In the present study, we tested combination immunotherapy of Ch FU-MK-1 with human lymphokine-activated killer (LAK) cells in vitro and in mice with severe combined immunodeficiency (SCID) bearing human MK-1-expressing tumors. In in vitro experiments, Ch FU-MK-1 effectively mediated antibody-dependent cell-mediated cytotoxicity (ADCC) against MK-1-expressing MKN-74 cells, which was completely blocked by an anti-FcR antibody. Since the apoptotic pathway as well as the necrotic pathway have been shown to be utilized in various cytotoxic effector mechanisms, we investigated the role of apoptosis in ADCC mediated by LAK cells and Ch FU-MK-1 against MKN-74 cells. The implication of the apoptosis during ADCC was demonstrated by means of both a terminal-deoxynucleotidyltransferase-mediated dUTP-biotin nick-end-labeling assay and a propidium iodide staining method. In vivo antitumor activity of combination treatment with LAK cells and Ch FU-MK-1 was estimated using SCID mice inoculated s.c. with MKN-74 cells. The i.v. administration of LAK cells and i.p. administration of Ch FU-MK-1 and interleukin-2 (IL-2) produced a marked growth inhibition of MKN-74 tumors in SCID mice. When the actual tumor weights were measured 16 days after initiation of treatment, more than 70% reduction was observed in the group receiving LAK cells plus Ch FU-MK-1 plus IL-2 as compared to the control untreated group. Together these results suggest that Ch FU-MK-1 may serve as a potentially useful immunotherapeutic reagent for human MK-1-expressing tumors.

Effect of choline on basal and stimulated acetylcholine release: an in vivo microdialysis study using a low neostigmine concentration

Using in vivo microdialysis, we examined the ability of choline (Ch) chloride (120 mg/kg i.p.) to amplify basal and stimulated acetylcholine (ACh) release from rat striatum in the presence of high (10 −5 M) and low (5 × 10 −8 M) neostigmine concentrations. High concentrations might suppress ACh release, and thus Ch dependence, by excessively stimulating presynaptic cholinergic receptors; alternatively, they could enhance Ch dependence by depriving the cholinergic terminals of Ch that would otherwise be formed intrasynaptically from the hydrolysis of ACh. Both basal and stimulated ACh release were found to be tetrodotoxin (TTX) sensitive. The concentration of neostigmine in the microdialysis fluid positively affected basal ACh levels, but had no effect on Ch levels. Ch administration significantly increased ACh release (to 136% of basal values; P < 0.01) in the presence of the low neostigmine concentration, but failed to significantly increase ACh release following local electrical depolarization of striatal neurons. In contrast, Ch failed to affect basal ACh release in the presence of the high neostigmine concentration, but did increase electrically evoked release to 408% of basal values, as compared with 250% in rats receiving saline instead of the Ch ( P < 0.05). Ch administration significantly increased microdialysate Ch levels in the presence of both of the neostigmine concentrations. Local administration of oxotremorine, a muscarinic agonist, to animals receiving the lower neostigmine concentration reduced basal ACh release and reduced the increase in basal release produced by Ch administration. These data affirm that systemic administration of Ch can enhance striatal ACh release, and show that the characteristics of this response are affected by the concentration of the cholinesterase inhibitor used in the experiment and by local muscarinic receptors.

NEONATAL DIRECT HYBERBILIRUBINEMIA (DHB) ASSOCIATED WITH CHLORAL HYDRATE (CH) DOSAGE

In order to investigate an apparent increase in the number of NICU newborns (NBs) with unexplained DHB, a retrospective analysis of all NBs admitted to the NICU over an 18 month period was conducted. The study revealed 11 newborns with undiagnosed DHB defined as direct bilirubin> 2 mg/dl or> 10% of the total bilirubin level. Four of the 11 NBs had identifiable factors which are known to cause DHB. Two of the 4 NBs had severe perinatal asphyxia with elevated liver enzymes and 2 NBs had prolonged hyperalimentation due to gastrointestinal adnormalities. All of the remaining 7 NBs (Group 1) did not have a diagnosable nor identifiable cause, but all had received CH 30-40 mg/kg q 4-6 h for sedation while on the ventilator. In these NBs, the DHB began to decrease within 2 days of the last CH dose. We next reviewed all charts of NBs who had received more than one dose of CH for sedation and did not have DHB (Group 2) .The table compares these two groups including the total CH dose/kg received. In summary, prolonged administration of CH appears to be associated with DHB in NBs in a dose response and temporal manner. Similar CH-induced hepatic toxicities have been reported in adults and animals. The human NB may be more sensitive to CH due to decreased metabolic clearance of CH and its active metabolite.

A teratological assessment of four trihalomethanes in the rat.

Four trihalomethanes were administered by gavage to Sprague-Dawley rats from day 6 to day 15 of gestation. Chloroform (Ch) was administered at levels of 100, 200 and 400 mg/kg and bromoform (Br), bromodichloromethane (BDCM) and chlorodibromomethane (CDBM) were administered at levels of 50, 100 or 200 mg/kg/day. A separate control was used for each compound. Maternal weight gain was depressed in all groups receiving Ch and at the highest dose levels of BDCM and CDBM. Ch administration caused decreased maternal hemoglobin and hematocrit values at all dose levels and also produced increased serum inorganic phosphorus and cholesterol at the highest dose. Liver enlargement was observed at all dose levels of Ch but in no other treatment groups. Evidence of a fetotoxic response was observed with Ch, CDBM and Br but not BDCM. No dose-related histopathological changes were observed in either mothers or fetuses as a result of treatment. None of the chemicals tested produced any teratogenic effects.

Immunosuppressive effects of methylglyoxal-bis(guanylhydrazone) on mouse bone marrow and spleen cells and their antagonism by spermidine

Changes in immunological function and in the activity of S-adenosylmethionine decarboxylase were studied in bone marrow and spleen cells from mice immunized with sheep red blood cells and given multiple doses of methylglyoxal-bis(guanylhydrazone) (CH 3-G) or CH 3-G in combination with spermidine. Inhibition by CH 3-G was found in the complement-dependent and complement-independent immune responses of cells from both tissue sources; however, this inhibition was greater and more persistent in bone marrow than in spleen cells. Co-administration of spermidine with CH 3-G completely prevented this inhibition in the spleen at all the time points studied, whereas in the bone marrow prevention appeared later and was lower in magnitude. The increase in the activity of S-adenosylmethione decarboxylase, a key enzyme in spermidine biosynthesis, was greater in bone marrow than in spleen after the administration of CH 3-G. Co-administration of spermidine with CH 3-G consistently reduced this increase in enzyme activity in spleen but not in bone marrow. In addition to prevention, appropriate scheduling of spermidine subsequent to CH 3-G resulted in reversal of both the immunosuppression and the increase in S-adenosylmethionine decarbooxylase activity produced by CH 3-G in spleen cells.

Huntington's disease: clinical and chemical effects of choline administration.

Choline (Ch) administration sequentially increases blood Ch, brain Ch, and brain acetylcholine (ACh) levels in the rat and might be useful in Huntington's disease, a brain disorder thought to be associated with deficient cholinergic tone. Ten patients with Huntington's disease took Ch orally (8 to 20 gm per day) after the extent of their disabilities had been documented by clinical examination, movies, and combined electromyogram-accelerometer recordings. Choline levels in blood and cerebrospinal fluid increased markedly during treatment with Ch, affirming that oral Ch administration increases the amount of ACh precursor delivered to the brain. Although some of the patients exhibited transient improvement in speech, balance, and gait, treatment with Ch failed to bring about consistent or lasting improvement in any of the subjects.

Synaptosomal transport and acetylation of choline

Acetylcholine (ACh) synthesis can be impaired by reduction of the availability of either of its precursors, choline (Ch) or acetylcoenzyme A (AcCoA). The high affinity transport of Ch is inhibited by hemicholinium-3 and this results in reduced synthesis of ACh (1–3). Under some circumstances ACh metabolism in the brain appears to be affected by parenteral (4) or dietary (5, 14) administration of Ch. The production of AcCoA can apparently be reduced by inhibition of the utilization of pyruvate or glucose, which also decreases the synthesis of ACh (6, 7). Recent experiments by Barker and Mittag (8, 9) led them to propose that the high affinity transport of Ch and the subsequent transfer of an acetyl group from AcCoA, catalyzed by Ch acetyltransferase (CAT), were directly coupled. We have tested this hypothesis by reducing the availability of AcCoA and measuring both the rate of transport of Ch by the high affinity system and the rate at which it is converted to ACh.

Microautoradiographic study of the distribution of methylmercuric (203) chloride in the Mallard duck ( Anas platyrhynchos)

Following oral administration of CH 3 203HgCl to adult Mallard ducks, a heavy concentration of labelled mercury was detected in the oesophageal mucosa, liver and kidney. The concentration of exposed silver grains in other tissues was only slightly greater than that of the background. At a cellular level a selective concentration of labelled mercury was seen only in the central nervous system, an accumulation being present in astrocytes in all regions of the brain and spinal cord and in ependymal cells. In one bird that received 0·684 mCi of 203Hg a selective accumulation of mercury was present in the cytoplasm of neurones of several brain nuclei and neurones in the spinal cord. The presence of methyl mercury in astrocytes may be related to functional changes in astrocytes.

Pharmacokinetics, Plasma Protein Binding; and Dosage of Chloramphenicol in Cattle and Horses

In 5 adult healthy cows and 8 adult healthy horses disappearance of chloramphenicol (Ch) from blood plasma after i.v. injection of 20 mg/kg and 40 mg/kg (3 horses) of a solubilized preparation of free Ch was followed by determining plasma concentrations by a colorimetric method. Binding of Ch to plasma proteins in the 2 species was measured by equilibrium dialysis. The results are expressed as the rate constant (k’2) and half time (t½) for elimination, and the binding capacity (β) and dissociation constant of the protein-drug complex (K3) for protein binding. From these data the doses for different dosage intervals have been calculated, assuming an average susceptibility of micro-organisms of 5.μg/ml. It is suggested that treatment of horses with Ch by the intravenous route might not be feasible because of rapid elimination. In cattle considerable difficulties might arise. It is concluded that the currently recommended doses for i.m.. administration of Ch in the 2 species may be inadequate. It is shown that this rapid elimination of the drug is achieved in both species by rapid transformation of Ch to polar metabolites, and that in cattle the major metabolite appearing in urine is a Ch-glucuronide.

Action of growth hormone and thyroxine on aortas of hypophysectomized dogs.

Young dogs were surgically hypophysectomized and maintained for eleven weeks postoperatively with age-matched normal controls. For three weeks prior to sacrifice, four hypophysectomized dogs were given daily injections of bovine growth hormone (GH, 0.2 mg./kg.) and another four were given daily injections of thyroxine (T4, 5 μg./ kg.). Aortas were removed, cleaned of adventitia and divided into three segments: arch, thoracic and abdominal. Each portion was analyzed for collagen, elastin, deoxyribonucleic acid (DNA), calcium, total mucopolysaccharides (MPS), hyaluronic acid (HA), heparan sulfate (HS), dermatan sulfate (DS) and chondroitin sulfate (GS). The arch and thoracic aortas of normal animals were found to contain more DNA, CS and elastin but less collagen than the abdominal aorta. Removal of the hypophysis resulted in an overall increase in elastin and DNA content and caused a decrease in all sulfated MPS. Administration of either CH or T4 to hypophysectomized dogs had a profound effect on the majority of constituents in all segments of aorta. GH returned the content of elastin, DS and CS toward normal in at least two of the three aortic segments. T4 returned the content of DNA, DS and CS toward normal in all segments. Moreover, T4 treatment caused significant reductions in collagen and HA contents of thoracic and abdominal segments. These results indicate that: (1) the composition of normal aorta varies with the segment studied; (2) the composition of the aorta is markedly affected by hypophysectomy, CH and T4 treatment; and (3) individual aortic segments show differential sensitivity to a given hormone.