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Olfactory influences on appetite and satiety in humans.

Odor stimuli play a major role in perception of food flavor. Food-related odors have also been shown to increase rated appetite, and induce salivation and release of gastric acid and insulin. However, our ability to identify an odor as food-related, and our liking for food-related odors, are both learned responses. In conditioning studies, repeated experience of odors with sweet and sour tastes result in enhanced ratings of sensory quality of the paired taste for the odor on its own. More recent studies also report increased pleasantness ratings for odors paired with sucrose for participants who like sweet tastes, and conversely decreased liking and increased bitterness for quinine-paired odors. When odors were experienced in combination with sucrose when hungry, liking was not increased if tested sated, suggesting that expression of acquired liking for odors depends on current motivational state. Other studies report sensory-specific satiety is seen with food-related odors. Overall, these studies suggest that once an odor is experienced in a food-related context, that odor acquires the ability to modify both preparatory and satiety-related components of ingestion.

Journal Article↗

Malignant catatonia with severe bronchorrhea and its response to electroconvulsive therapy.

A 21-year-old female presented excitement, auditory hallucination, monologue, and insomnia. After 1 week of risperidone administration, she showed hyperthermia, salivation, and muscle rigidity. Risperidone was discontinued, but stupor, convulsions, and respiratory distress developed. In the intensive care unit where she was transferred, catatonic symptoms such as stupor or excitement, catalepsy, and negativism were prominent. In addition, severe bronchorrhea causing respiratory failure was observed. Her catatonic symptoms, hyperthermia, and bronchorrhea resolved by ECT. After recovery, affective flattening, alogia, and avolition remained. The final diagnosis was MC associated with schizophrenia. This report suggests that MC may be complicated by severe bronchorrhea, but this condition responds to ECT.

Adult↗

Hypotension, bradycardia and syncope caused by honey poisoning.

Honey intoxication, a kind of food poisoning, can be seen in the Black Sea region of Turkey and in various other parts of the world as well. In this study, 66 patients were hospitalized with a variety of symptoms including nausea, vomiting, salivation, dizziness, weakness, hypotension, bradycardia and syncope several hours after the ingestion of small amounts of honey. All patients had hypotension, and majority had bradycardia. These features resolved completely in 24 h with i.v. fluids and atropine, and none died. In conclusion, honey poisoning should be taken into consideration in the differential diagnosis of acute myocardial infarction and in the patients with vomiting, hypotension and bradycardia.

Adolescent↗

Clinical audit of subjects with snoring & sleep apnoea/hypopnoea syndrome fitted with mandibular repositioning splint.

Snoring and obstructive sleep apnoea/hypopnoea syndrome (OSAHS) are often treated with mandibular repositioning splints (MRS), but the efficacy and satisfaction of them has not been comprehensively addressed. A survey on the use of and satisfaction with MRS was posted to 177 patients referred by a hospital orthodontic department for custom-fitting of a MRS. Data were analysed using non-parametric techniques. The response rate was 81% (n=144). Responders (30F, 114M) had mean (SD) age of 51 (11) years, apnoea+hypopnoea index (AHI) of 24 (21) per hr and Epworth Score of 10 (5) at diagnosis, and had been supplied with their MRS a median 7 (IQR 5-11) months previously. Fifty of the 144 patients (35%) had been offered continuous positive airway pressure (CPAP) treatment but had declined or abandoned this. Self-reported MRS use was 5 (2) h/night, with 74 of the 144 patients (51%) continuing to use MRS at least occasionally at a median 7 months after fitting. Survival analysis showed 12% still using MRS at 12 months. Epworth score fell slightly with MRS therapy [-2.4 (3.5); P=0.005] and 7 daytime and 2 nocturnal symptoms improved in MRS users (all P<0.05). Marital satisfaction did not change with MRS. Problems preventing MRS use in 70 non-users included: non-retention (n=12), sore mouth (n=13) or jaw (n=7), difficulties falling asleep (n=10) or breathing (n=7), excessive salivation (n=4), dental damage (n=4) and other problems (n=3). Continued use of MRS therapy was associated with a higher number of teeth, low marital satisfaction perceived by partners and greater improvement in symptoms reported by patients and partners. Continuance with MRS may be low and linked to tolerance problems.

Continuous Positive Airway Pressure↗

Pathophysiology of gastroesophageal reflux disease.

From a pathophysiologic viewpoint, GERD results from the excessive reflux of gastric contents into the distal esophagus. Under normal conditions, this is prevented as a function of the antireflux barrier at the EGJ, the integrity of which is dependent on the delicate interplay of a host of anatomic and physiologic factors, including the integrity of the LES, TLESR, and anatomic degradation of the EGJ inclusive of but not limited to hiatus hernia. Considerable investigative focus is aimed at describing the subtle aberrations of the EGJ that may contribute to the root causes of GERD. The net result is an increased number of reflux events, an increasing diversity of potential mechanisms of reflux, and a diminished ability of the stomach to selectively vent gas, as opposed to gas and gastric juice, during TLESR. Once reflux occurs, the duration of resultant esophageal acid exposure is determined by the effectiveness of esophageal acid clearance, the dominant determinants of which are peristalsis, salivation, and, again, the anatomic integrity of the EGJ. Approximately half of patients who have GERD have abnormal acid clearance and the major contributor to this is hiatus hernia. Abnormalities of acid clearance probably are the major determining factor influencing which patients who have GERD are most prone to developing esophagitis as opposed to symptomatic GERD. In summary, GERD is a multifactorial process involving physiologic and anatomic abnormalities. These abnormalities exhibit a complicated interplay that degrades the ability of the EGJ to contain gastric juice within the stomach and to clear the esophagus of gastric juice effectively once reflux has occurred.

Disease Progression↗

Disposition of lead (Pb) in saliva and blood of Sprague-Dawley rats following a single or repeated oral exposure to Pb-acetate.

Biological monitoring for lead (Pb) is usually based upon a determination of blood Pb concentration; however, saliva has been suggested as a non-invasive biological matrix for assessing exposure. To further evaluate the potential utility of saliva for biomonitoring, the disposition of Pb was evaluated in whole blood (WB), red blood cells (RBC), plasma, parotid gland, bone, and saliva following either a single oral dose of 100mg Pb-acetate/kg body weight in rats or approximately 1-week after 5 sequential daily oral gavage doses of 1, 10, or 100mg Pb-acetate/kg/day. Saliva volume, pH, total saliva protein, and alpha-amylase activity were also determined. At specified times post-dosing groups of animals were anesthetized and administered pilocarpine to induce salivation. Saliva was collected, the animals were humanely sacrificed, and tissue samples were likewise collected, weighed, and processed for Pb analysis. Following a single dose exposure to Pb-acetate, Pb was detectable in all samples by 30 min post-dosing. For both the single and repeated dose treatments the concentration of Pb was highest in WB and RBC relative to plasma and saliva. However, the Pb rapidly redistributed (within 5-days post-treatment) from the blood into the bone compartment based on the substantial decrease in WB and RBC Pb concentration, and the concurrent increase in bone Pb following repeated exposure at all dose levels. Although there is clear variability in the observed Pb concentrations in plasma and saliva, there was a reasonable correlation (r(2)=0.922) between the average Pb concentrations in these biological matrices, which was consistent with previous observations. The single oral dose of Pb-acetate resulted in a decrease in salivary pH which recovered by 24h post-dosing and a decrease in alpha-amylase enzyme activity which did recover within 5-days of ceasing exposure. It is currently unclear what impact these slight functional changes may or may not have on Pb salivary clearance rates. These results demonstrate a feasibility to rapidly detect Pb in saliva and suggest that saliva may correlate best with plasma Pb concentration.

Animals↗

Vipera palaestinae envenomation in 327 dogs: a retrospective cohort study and analysis of risk factors for mortality.

Vipera palaestinae (Vp), formerly a subspecies of the near east viper Vipera xanthina, is the most common poisonous snake in Israel and neighbouring countries (Jordan, Lebanon and Syria), and is responsible for most envenomations in humans and domestic animals. Hospital records were retrospectively reviewed for confirmed cases of Vp envenomations in dogs over a 13-year period and 327 cases were included in the study. Most envenomations occurred between May and October, and between 02:00 and 10:00 PM. The most frequent clinical signs included: local swelling and oedema (99.6%), viper teeth penetration marks (51%), tachypnoea (50%), panting (44%), increased body temperature (19.2%), tachycardia (>160/min, 19%), salivation (18%) and lameness (15.6%). Common haematological findings included: increased haematocrit (47%), increased haemoglobin concentration (45%), leucocytosis (39%), and thrombocytopenia (30%). The prothrombin time and activated partial thromboplastin time were prolonged in 68 and 21% of the dogs, respectively. Blood biochemistry abnormalities included increased activities of muscle enzymes, hyperglycaemia, hyperbilirubinaemia, hyperglobulinaemia and hypocholesterolaemia. The mortality rate was 4% (13 dogs). The following variables were significantly (p < 0.05) associated with mortality: body weight below 15 kg (p = 0.01), limb envenomation (0.008), envenomation at night (p = 0.025), severe lethargy (P < 0.001), hypothermia (p = 0.04), systemic bleeding (p = 0.001), shock (p = 0.007), dyspnoea (p = 0.002), tachycardia (p = 0.002), thrombocytopenia (p = 0.02), and glucocorticosteroid therapy (p = 0.002). Dogs younger than 4 years had a lower death risk (p = 0.01). The association of steroid therapy with increased mortality suggests that the use of steroids in Vp envenomations may be harmful. Specific antivenom therapy (10 ml/dog) was not associated with a higher survival rate, thus its use, dose and timing of administration should be further investigated.

Animals↗

Blockade of neuronal nitric oxide synthase abolishes the toxic effects of Tx2-5, a lethal Phoneutria nigriventer spider toxin.

The primary goal of this study was to determine whether Tx2-5, a sodium channel selective toxin obtained from the venom of the spider Phoneutria nigriventer, produced penile erection by means of nitric oxide mechanism. Toxin identity was analyzed by MALDI-TOF, ES-MS and N-terminal amino acid sequencing. Pretreating mice with the non-selective nitric oxide synthase (NOS) inhibitor N(omega)-Nitro-L-arginine methyl ester hydrochloride (L-NAME) and the selective neuronal-NOS inhibitor 7-Nitroindazole (7-NI) prior to Tx2-5 i.p. (10 microg/25 g mouse) injection challenged the hypothesis above. Controls were injected with the D-isomer or DMSO or saline. Results demonstrated that L-NAME inhibited penile erections in about half the animals treated, while 7-NI completely abolished this effect. Interestingly 7-NI also abolished all the other symptoms of intoxication induced by Tx2-5, including salivation, respiratory distress and death. Tx2-5 killed all the animals of the control group and no one in the 7-NI-treated group. We conclude that (1) intraperitoneal injections of Tx2-5 induce a toxic syndrome that include penile erection, hypersalivation and death by respiratory distress or pulmonary edema; (2) pretreatment with the non-selective NOS inhibitor L-NAME reduces the penile erection and partially protects from the lethal effects of Tx2-5; (3) pretreatment with the nNOS-selective inhibitor 7-NI completely abolishes all the toxic effects of Tx2-5, including penile erection and death suggesting that nNOS is the major player in this intoxication; (4) toxins from other animals that affect sodium channels in the same way as Tx2-5 and induce similar toxic syndromes may have as a major common target, the activation of nitric oxide synthases.

Analysis of Variance↗

Primary structure, behavioral and electroencephalographic effects of an epileptogenic peptide from the sea anemone Bunodosoma cangicum.

The primary structure of cangitoxin (CGX), a 4958 Da peptide from the sea anemone Bunodosoma cangicum, was determined: GVACRCDSDGPTVRGNSLSGTLWLTGGCPSGWHNCRGSGPFIGYCCKK. CGX contains all the 11 residues that are conserved and the 5 that are conservatively substituted within or between the type 1 and type 2 sequences of sea anemone peptides with specific action on voltage-sensitive sodium channels. Furthermore, it also has 6 identities (Asp9, Arg14, Asn16, Leu18, Trp33 and Lys48) and 1 homology (Arg36) in the 8 residues of the pharmacophore of the sea anemone ApB which are essential for interaction with mammalian sodium channels. The intrahippocampal injection of CGX induces several sequential behavioral alterations--episodes of akinesia alternating with facial automatisms and head tremor, salivation, rearing, jumping, barrel-rolling, wet dog shakes and forelimb clonic movements--and the electroencephalography analysis shows that they were followed by important seizure periods that gradually evolved to status epilepticus that lasted 8-12 h, similar to that observed in the acute phase of the pilocarpine model of epilepsy. These results suggest that CGX may be an important tool to develop a new experimental model of status epilepticus which may contribute to understanding the etiology of epilepsy and to test the effects of new antiepileptic drugs.

Amino Acid Sequence↗

Castor bean (Ricinus communis) toxicosis in a sheep flock.

This paper describes clinical, laboratory and pathological findings of sheep, which is intoxicated with castor bean. The source of intoxication was a miscellaneous garden waste. Forty-five animals showed clinical toxicosis and 17 died. The clinical signs included weakness, salivation, profuse watery diarrhoea, dehydration, mydriasis, teeth grinding, hypothermia and recumbency. The most significant haematological and biochemical findings were a high haematocrit, high concentration of serum BUN, creatinine and phosphorus and high activity of serum CK and AST. Pathology revealed severe gastroenteritis, cardiac haemorrhage and necrosis, hepatic necrosis and acute tubular necrosis in kidneys. Treatment included symptomatic and supportive care with fluid therapy and cathartic administration.

Abomasum↗

An update of the etiology and management of xerostomia.

Salivary gland disease gives rise to salivary gland enlargement, pain, and prolonged xerostomia (dry mouth). Xerostomia is the most common long-standing problem for the majority of affected patients. There are many causes of dry mouth, with long-standing xerostomia being a particular problem in Sjögren's syndrome and after radiation to the head and neck region. Xerostomia is usually managed with saliva substitutes, but a large number of potential systemic therapies of long-standing xerostomia now exist. Some-particularly immunosuppressants-are of fundamental interest for the potential reduction of gland damage in Sjögren's syndrome but as yet are of limited clinical usefulness. Others, particularly pilocarpine and cevimeline, are, or have the potential to be, clinically useful in stimulating salivation by virtue of their action on cholinergic receptors.

Cholinergic Agents↗

False-positive xerostomia following radioactive iodine treatment: case report.

Radioactive iodine (131I), used in the treatment of differentiated thyroid carcinoma, is known to cause both short-term and long-term radiation damage to the salivary glands. The injury appears as glandular swellings and/or decreased salivation with 131I dosage and passage of time playing significant roles. A case report is presented to alert the profession to the existence of patients who have received 131I therapy and who complain shortly thereafter of xerostomia, but following a thorough examination are found to represent a group of false-positives. Emphasis is placed on the diagnostic techniques used in the differential diagnosis.

Adult↗

Toxic effects seen in a herd of beef cattle following exposure to ash residues contaminated by lead and mercury.

Lead poisoning was diagnosed in three cattle along with increased mercury levels in the liver and kidney tissues of two of these animals. The clinical signs were different in each case and included salivation, anorexia, delayed menace response, delayed withdrawal reflex, head pressing, localized muscle fasciculation, reduced tongue tone, ataxia, rumen atony and seizures. Blood lead concentration was increased in all three cases to 0.76, 0.37 and 0.454ppm. Post mortem changes characteristic of lead poisoning were only recognized in one case and included cerebro-cortical oedema, cortical neuronal necrosis and endothelial proliferation, especially at the tips of the cerebral gyri. The animals were poisoned by ingestion of lead-contaminated ash residues from a bonfire. The abnormal levels of mercury in the liver and kidney tissues of two animals may also be at least partly attributable to the intake of the metal in the ash residues. The levels of mercury in the three samples from the ash residue were relatively low (1.31, 0.7 and 2.1ppm).

Animals↗

Increased fluid secretion after adenoviral-mediated transfer of the human aquaporin-1 cDNA to irradiated miniature pig parotid glands.

The treatment of most head and neck cancer patients includes ionizing radiation (IR). Salivary glands in the IR field suffer irreversible damage. Previously, we reported that adenoviral (Ad)-mediated transfer of the human aquaporin-1 (hAQP1) cDNA to rat submandibular glands following IR restored salivary flow to near normal levels. It is unclear if this strategy is useful in larger animals. Herein, we evaluated AdhAQP1-mediated gene transfer after parotid gland IR (20 Gy) in the miniature pig. Sixteen weeks following IR, salivation from the targeted gland was decreased by >80%. AdhAQP1 administration resulted in a dose-dependent increase in parotid salivary flow to approximately 80% of pre-IR levels on day 3. A control Ad vector was without significant effect. The effective AdhAQP1 dose was 2.5 x 10(5) pfu/microl infusate, a dose that leads to comparable transgene expression in murine and minipig salivary glands. Three days after Ad vector administration little change was observed in clinical chemistry and hematology values. These findings demonstrate that localized delivery of AdhAQP1 to IR-damaged salivary glands increases salivary secretion, without significant general adverse events, in a large animal model.

Adenoviridae↗

Relationships between medication intake, complaints of dry mouth, salivary flow rate and composition, and the rate of tooth demineralization in situ.

The aim of this study was to describe the relationships between the rate of tooth demineralisation and medication intake, subjective feeling of dry mouth, saliva flow, saliva composition and the salivary level of lactobacilli. The study group consisted of 28 subjects that were divided into three groups according to their unstimulated whole saliva flow rate. Group 1 had an unstimulated saliva low rate < or =0.16 ml/min (n=10), group 2 had one from 0.17--0.30 ml/min (n=9), and group 3 had one >0.30 ml/min (n=9). The rate of tooth demineralization was determined as mineral loss assessed by quantitative microradiography of human root surfaces, exposed to the oral environment for 62 days in situ. The unstimulated and stimulated saliva flow rates, pH, bicarbonate, calcium, phosphate, and protein concentrations, as well as the degree of saturation of saliva with hydroxyapatite and the saliva buffer capacity were determined. The results showed that almost all subjects developed demineralization, albeit at highly varying rates. Eighty-five percent of the subjects in group 1, 33% of the subjects in group 2, and 0% of the subjects in group 3 developed mineral loss above the mean mineral loss for all the root surfaces in this experiment. Futhermore, group 1 differed significantly from groups 2 and 3 in having a higher medication intake, a more pronounced feeling of dry mouth, lower stimulated saliva flow rate, lower stimulated bicarbonate concentration, lower unstimulated and stimulated compositional outputs (bicarbonate, calcium, phosphate, and protein), and a higher Lactobacillus level. The best explanatory variable for high mineral loss in this study was a low unstimulated saliva flow rate. In conclusion, our results suggest that an unstimulated salivary flow rate < or =0.16 ml/min as described by Navazesh et al. (1992), is a better indicator of increased caries risk due to impaired salivation, than the currently accepted definition of hyposalivation (unstimulated saliva flow rate < or =0.10 ml/min), which relates to the function of the salivary glands (Sreebny, 1992).

Adult↗

Chemical characterization of the two forms of epidermal growth factor in murine saliva.

Extracts of murine salivary glands contain two molecular forms of epidermal growth factor, EGF I and EGF II (Petrides, P.E., Levine, A.E., Shooter, E.M. in: Peptides: - Synthesis, Structure and Function (Rich, D.H., Gross, E.eds.) p. 781 (1981]. We have identified both molecules not only in salivary gland extracts but also in saliva using only reverse phase liquid chromatography methodology. EGF I and II were isolated from submaxillary gland extracts in a ratio of 3:1 regardless of whether the classical isolation procedure or our rapid RPLC based technique was used. Both molecular forms were present in the same ratio in saliva of mice of both sexes when salivation was induced by epinephrine treatment of the animals. As judged by amino acid analysis and N-terminal sequencing salivary EGF I corresponds to the 53 amino acid sequence of murine EGF and EGF II is Des-ASN-EGF. The observation that EGF and Des-ASN-EGF are consecreted into saliva upon epinephrine stimulation implies a physiological role of EGF II which may be related to the high molecular weight EGF-complex.

Amino Acid Sequence↗

Double-blind comparison of olanzapine versus clozapine in schizophrenic patients clinically eligible for treatment with clozapine.

BACKGROUND: The treatment of schizophrenic patients who fail to respond to adequate trials of neuroleptic drugs is a major challenge. Clozapine has been one treatment option; however, it is not universally effective and is limited in its use by safety concerns. With the introduction of newer agents, their performance relative to clozapine is of great clinical interest. METHODS: The primary objective of this study was to evaluate the efficacy and safety of olanzapine versus clozapine among treatment resistant DSM-IV schizophrenic patients. The study was primarily designed to demonstrate the "noninferiority" of olanzapine compared to clozapine after 18 weeks of double-blind treatment. Conclusions were based on the one-sided lower 95% confidence limit about the treatment effect observed from the primary efficacy variable (Positive and Negative Syndrome Scale [PANSS] Total). RESULTS: Mean changes from baseline to end point in PANSS Total score, using a last observation carried forward technique, showed that both agents were comparably effective in neuroleptic resistant patients, i.e., demonstrated the "noninferiority" of olanzapine when compared to clozapine. Overall, significantly fewer olanzapine-treated patients (4%) discontinued for an adverse event than their clozapine-treated (14%) counterparts (p =.022). Among spontaneously reported adverse events, increased salivation, constipation, dizziness, and nausea were reported significantly more often among clozapine-treated patients, whereas only dry mouth was reported more often among olanzapine-treated patients. CONCLUSIONS: Olanzapine was demonstrated to be noninferior to clozapine and better tolerated among resistant schizophrenic patients clinically eligible for treatment with clozapine.

Adult↗

Hippocampal transection attenuates kainic acid-induced amygdalar seizures in rats.

Since the dorsal and ventral hippocampus in the rat may act differently from one another in limbic seizures, we studied effects of orthogonal transection between the dorsal and ventral hippocampus upon kainic acid-induced amygdalar seizures. A total of 26 rats were divided into three groups. Ten rats underwent transection using a modified wire knife (transection group); 16 others were untransection group (n=10) and controls (n=6). All the rats then underwent stereotactic implantation of electrodes in the left amygdala (LA), left dorsal hippocampus (LdH), left ventral hippocampus (LvH), and the left sensorimotor cortex (LCx). A stainless steel cannula also was introduced into the LA. Rats except controls later received 1.0 microg of kainic acid (KA) via the cannula. Controls received phosphate buffer solution alone. In the untransection group, multiple spike discharges in the LA immediately propagated concurrently to the LvH and LdH. Propagation involved the LCx to become status epilepticus 1 to 2 h after KA injection. Seizures, characterized by mastication, salivation, facial twitching, forelimb clonus, and sometimes rearing and falling, lasted 1 to 2 days. Microscopic examination revealed severe neuronal cell damage in the LA, LvH, and LdH. In the transection group, multiple spike discharges initiated from the LA and were propagated to LvH, but LdH as well as LCx involvement was slight. Status epilepticus involved only the LA and LvH 1 to 2 h following KA injection. Seizures subsided within 24 h, showing no ictal manifestations except for aggressiveness. Overall, seizures were weak and transient compared with those in controls. Histologically, hippocampal neuronal damage was slight, but damage to amygdalar neurons was similar to that in untransection group. No electroclinical and histological changes were seen in controls. These results indicated that connections between the dorsal and ventral hippocampus are important for full development of KA-induced amygdalar seizures.

Amygdala↗