Omar R. Tumilasci

Quantitative Study of Salivary Secretion in Parkinson's Disease

We examined basal and reflex salivary flow rate and composition in 46 patients with Parkinsons disease (PD), both in off and on conditions, compared to 13 age‐matched controls without underlying disease or treatment affecting autonomic function. Whole saliva was collected 12 hours after withdrawal of dopaminergic drugs and at the peak of levodopa‐induced motor improvement. Twenty‐three of the 46 PD patients had received domperidone a week before the study. Basal salivary flow rate was significantly lower in PD patients in the off state compared to controls (P < 0.005). Levodopa increased salivary flow rate (P < 0.05) both in the domperidone‐pretreated and untreated groups. Citric acid stimulated salivary flow rate in both the off and on states in PD patients. This effect was higher in the domperidone‐pretreated patients. Salivary concentration of sodium, chloride, and amylase was higher in PD patients than in controls and was not affected by levodopa or domperidone treatment. Levodopa stimulates both basal and reflex salivary flow rate in PD. The mechanism appears to be central, as the effect is not blocked by domperidone. Domperidone may have a peripheral effect that potentiates reflex salivary secretion. Salivary composition is abnormal in PD and is not affected by levodopa treatment.

Salivary testosterone: a reliable approach to the diagnosis of male hypogonadism.

Objective  This study was to demonstrate that Sal‐T is a reliable biomarker of androgen status in the diagnosis of male hypogonadism.

Assessment of salivary urea as a less invasive alternative to serum determinations

Objective. Experimental studies describe how urea is excreted through salivary glands and correlates with serum levels independently of salivary flow rate. This study confirms that salivary urea (SaU) is a reliable biomarker of uraemic state. In order to validate the SaU methodology, the following factors were taken into account: the independence of urea levels from saliva flow rate in healthy subjects and patients with chronic renal failure and the agreement between SaU and serum urea (U) levels in the entire population. In addition, reference intervals and cut‐off values for SaU and U were established. Material and methods. Urea levels were determined in 268 matched whole saliva (SaU) and serum (U) samples obtained simultaneously from 78 healthy individuals and 154 patients with chronic renal failure. A serum enzymic colorimetric assay was adapted to SaU determinations. Results. SaU was independent of salivary flow rate. The agreement between SaU and U was confirmed by Bland‐Altman analysis with a significant correlation between them (r = 0.91, p = 0.0001). The reference interval of SaU ranged from 1.66 to 7.5 mM. The cut‐off values for SaU and U were 7.5 mM and 8.2 mM, respectively (sensitivity and specificity 100 % for both). Conclusions. SaU testing is harmless and useful for ruling out azotemic states in outpatients. Our results support the inclusion of SaU as a diagnostic test in the clinical laboratory.

Diagnostic value of salivary cortisol in Cushing's syndrome (CS).

Objective  The diagnosis of Cushings syndrome (CS) remains a challenge in clinical endocrinology. The aim of this study was to determine the reproducibility and diagnostic value of late‐night salivary cortisol (SAF23) for CS and its utility along the follow‐up of treated patients. In addition, using the same radioimmunoassay reactives, the cut‐off values for saliva and serum cortisol, assessed synchronically after the overnight 1 mg dexamethasone suppression test (DST), were defined.

Hyposialorrhea as an early manifestation of Parkinson disease

We sought to determine whether hyposialorrhea is an early manifestation of Parkinson disease (PD). We measured basal and citric acid stimulated secretion of whole saliva in 20 patients with early stage (Hoehn-Yahr I-II) PD who had motor symptoms for less than 1 year and were on no medication and 11 age matched controls. Compared to controls, PD patients had significant reduction of both basal (0.0964+/-0.08 vs 0.293+/-0.112 ml/min, p<0.001) and reflex (0.263+/-0.213 vs 0.537+/-0.313 ml/min, p<0.001) salivary secretion. Our findings confirm that hyposialorrhea is an early autonomic manifestation of PD.

Diagnostic value of salivary cortisol in end stage renal disease

OBJECTIVES Salivary cortisol has been proposed a surrogate marker for free serum cortisol measurements. The aim of this study was to ascertain the diagnostic value of basal and stimulated salivary cortisol for the detection of adrenal insufficiency (AI) in hypotensive end stage renal disease (ESRD) patients. Basal salivary cortisol and basal total serum cortisol were studied in order to determine the accuracy of both biomarkers in predicting AI. PATIENTS AND METHODS Twenty-nine ESRD patients with sustained hypotension were investigated for possible AI. Salivary cortisol was assessed at baseline and 30min after 25microg ACTH i.m. (LDTs). The dosage of salivary aldosterone was performed in salivary cortisol hypo-responders. Basal blood samples were drawn for steroids, renin and ACTH measurements. RESULTS A clear separation between patients with normal and impaired adrenal function was obtained through salivary cortisol levels at 30min after ACTH. AI was detected in six cases (21%) through impaired salivary cortisol responses; stimulated salivary aldosterone helped to differentiate primary (n=3) from secondary AI (n=3). ROC curves showed that cutoff values for basal SAF < or =4.4nM and serum cortisol < or =232.0nM suggest AI (sensitivities: 93% and 69%; specificities: 86.4% and 91%, respectively). CONCLUSIONS We conclude that ACTH stimulated SAF is an accurate biomarker for the diagnosis of AI in hypotensive ESRD patients. Neither basal salivary cortisol nor serum cortisol showed 100% sensitivities for the detection of AI.

Studies on the mechanisms of L-dopa-induced salivary secretion

Systemic administration of L-dopa and dopamine elicited a marked and sustained secretory response in the rats submaxillary glands. These effects were blocked by pretreatment with phentolamine plus propranolol. Acute unilateral sympathectomy (decentralization or denervation) reduced the response to L-dopa by about 41-48%. But it left unchanged the secretory response to dopamine. Chemical sympathectomy by hexamethonium caused a similar reduction (45%) in the secretory response to L-dopa while parasympathectomy was unable to modify the salivary secretion caused by L-dopa or dopamine. Pretreatment with haloperidol reduced the salivary secretion to L-dopa in normal animals (unoperated glands), while the response to dopamine was unaffected. On the other hand, haloperidol did not alter the salivary response to L-dopa in animals with surgical sympathectomy (denervation) as compared to the same animals treated with L-dopa alone. From this study we conclude that the salivary secretion induced by L-dopa is mediated by both central and peripheral mechanisms. Dopaminergic receptors may be involved in the central effect and alpha- and beta-receptors in the peripheral response.

Selective increase ofα1-adrenoceptors and muscarinic cholinergic receptors in rat cerebral cortex after chronic haloperidol

The effect of chronic administration of haloperidol on alpha 1-, alpha 2-, and beta-adrenoceptors, cholinergic muscarinic, GABAA and benzodiazepine receptors in the cerebral cortex of the rat was investigated. Doses of 0.3 and 2 mg/kg of haloperidol during 7 days increased markedly the density of alpha 1-adrenoceptors without changes in affinity. The alpha 2- and beta-adrenoceptors were not modified after neuroleptic administration. The number of muscarinic receptors were also increased after haloperidol treatment (2 mg/kg/day). However, the GABAA and benzodiazepine binding sites remained unchanged. In the brainstem an increment in the alpha 1-, but not the beta-adrenoceptors was observed. The well known increase in the dopamine receptors in the striatum was confirmed. These observations demonstrate a multireceptor effect of haloperidol in the cerebral cortex.

The role of the caudate-putamen nucleus in salivary secretion induced by L-DOPA

Experiments were performed in rats of the Wistar strain anesthetized with alpha-chloralose (100 mg/kg). Electrolytic lesion of either components of the striopallidal complex (corpus striatum, globus pallidus or entopeduncular nucleus) reduced the sensory response to L-DOPA in the contralateral submaxillary glands. Damage to other neural structures, directly or indirectly related to the striopallidal system, left the salivary response unaffected. These structures were: substantia nigra, cerebral cortex, ventromedial and center median-parafascicular thalamic nuclei, nucleus accumbens and posterior hypothalamic areas, including the medial forebrain bundle and lateral habenular nucleus. However, lesions placed in H1-H2 fields of Forel and reticular formation, lateral to the periaqueductal gray, reduced the salivary response in the contralateral glands. This effect was similar to that observed in animals with lesions of the striopallidal complex. From this study, it is concluded that the striatum is the target area for the central effect of L-DOPA on salivary secretion, by activation of pathways descending through the fields of Forel and mesencephalic reticular formation to the contralateral lower brain stem.

Chronic haloperidol causes increase in salivary response and α1-adreneceptors in submandibular gland of the rat

The effect of chronic haloperidol on the receptor-secretion coupling of the submandibular glands of the rat was studied. After injection of 2 mg/kg haloperidol daily for 7 days, the dose-response curve to L-noradrenaline was displaced to the left, with lowering of the threshold and enhancement of the maximal response. This was accompanied by a 73% increase in α1-adrenoceptors in the glands. The effect was selective, since no changes were observed in α2- and β-adrenoceptors.