Metallic insignia in primary teeth A biomarker for Autism Spectrum Disorders

Background: Lead accumulations have been found in teeth and related to behavior deficits in children, but there is a dearth of studies in exploring the role of zinc and manganese dysregulations in autism spectrum disorders (ASD) using the primary tooth as biomarker. Aims: The objectives of the study were to evaluate and compare the concentrations of zinc and manganese in the primary teeth serving as biomarker, in typically developing children and children with ASD. Settings and Design: Twelve primary incisors indicated for extraction were collected from children between the age group 6 and 9 years, for the study. Six primary incisors were obtained from children who had been diagnosed with ASD (study group). The other six teeth were obtained from typically developing children, in the similar age group. Methods: The primary incisors obtained were analyzed for metal concentrations using the technique Inductively Coupled Plasma Optical Emission Spectrometry. Statistical Analysis: This study was statistically analyzed by student's t-test. Results: It was observed that there are significant differences in metal concentrations found between tooth samples of ASD children and typically developing children. Zinc concentrations were double and manganese concentrations were three times, in teeth of ASD children group as compared to the children in the control group. Conclusions: Results of the current study indicate that there are considerable differences in concentrations of zinc and manganese between the two groups and support the contention that there might be an association between metal exposures of a pregnant mother and child during early years of childhood and incidence of ASD.

Clinical Study of Headache in Relation to Sinusitis and its Management.

Aim: To study relation of headache with sinusitis and its management. Material and methods: Patients clinically presenting with headache were selected. Only patients with headache due to rhinogenic causes were subjected to X-ray paranasal sinuses (PNS) and diagnostic nasal endoscopy (DNE) and were followed up to evaluate management. Results: Majority of the patients were of age group 21-30 years and it is more predominant in males. Majority of the patients with headache had deviated nasal septum (DNS) (28.9%), acute sinusitis (28.9%), osteomeatal complex disease (24.63%); few patients had nasal polyp (8.69%), allergic rhinitis (5.79%) and rarely patients had atrophic rhinitis (2.89%). Headache was localized in forehead (43.4%), more than one site (34.7%) in majority of cases and few number of patients had headache at glabella (13.04%) and top of head (8.69%). Majority of the patients who underwent antral washout were not relieved, so they underwent functional endoscopic sinus surgery (FESS), which gave dramatic results in improving symptoms including headache. Conclusions: Headache is nearly a universal human experience. The lifetime incidence of headache is estimated to be at least 90%. To know whether the headache is sinogenic or not, the patient is first assessed clinically and then radiological investigations (X-ray PNS) are done. Role of FESS is huge and ultimately it is FESS that is the cure for headache due to rhinogenic causes.

Antinociceptive action of FK506 in mice.

Immunophilins are abundantly present in the brain as compared to the immune system. Immunophilin-binding agents like FK506 are known to inactivate neuronal nitric oxide synthase (nNOS) by inhibiting calcineurin and decrease the production of nitric oxide. Nitric oxide is involved in the mediation of nociception at the spinal level. In the present study, the effect of FK506 on the tail flick response in mice and the possible involvement of NO-L-arginine pathway in this paradigm was evaluated. FK506 (0.5, 1 and 3 mg/kg, ip) produced a significant antinociception in the tail flick test. Nitric oxide synthase (NOS) inhibitor L-NAME significantly and dose dependently (10-40 mg/kg, ip) potentiated the FK506 (0.5 mg/kg)-induced antinociception. On the other hand, NOS substrate L-arginine (100, 200 and 400 mg/kg) inhibited the FK506-induced antinociception in a dose-dependent manner. Concomitant administration of L-NAME (20 and 40 mg/kg) with L-arginine (200 mg/kg) blocked the inhibition exerted by L-arginine on the FK506-induced antinociception. Thus, it was concluded that NO- L-arginine pathway may be involved in the FK506-induced antinociception in tail flick test.

D2-dopamine receptor and alpha2-adrenoreceptor-mediated analgesic response of quercetin.

Quercetin, a bioflavonoid (100-300 mg/kg) produced dose dependent increase in tail-flick latency, the analgesic effect being sensitive to reversal by naloxone (1 mg/kg). Prior treatment with haloperidol (1 mg/kg), D1/D2 receptor antagonist haloperidol, sulpiride (50 mg/kg), a selective D2 receptor antagonist, yohimbine (5 mg/kg), a alpha2-adrenoreceptor antagonist but not by SCH 23390 a, selective D1 receptor antagonist blocked this response. Apomorphine (1 mg/kg) a mixed D1/D2 dopamine receptor agonist, and quinpirole (0.5 mg/kg), a selective D2 receptor agonist also produced antinociception, that was reversed by haloperidol (1 mg/kg), sulpiride (50 mg/kg), but not by yohimbine (5 mg/kg). The antinociceptive action of quercetin (200 mg/kg) was potentiated by D2 agonist quinpirole (0.2 mg/kg). Dopamine D1 receptor agonist SKF38393 (10 and 15 mg/kg) failed to alter the antinociceptive effect of quercetin (200 mg/kg). Quercetin (200 mg/kg) reversed reserpine (2 mg/kg-4 hr) induced hyperalgesia, which was reversed by sulpiride but not by yohimbine. Thus, a role of dopamine D2 and alpha2-adrenoreceptors is postulated in the antinociceptive action of quercetin.

FK506 as effective adjunct to L-dopa in reserpine-induced catalepsy in rats.

Reserpine-induced catalepsy is a widely accepted animal model of Parkinson's disease. In the present study reserpine (2.5 mg/kg, ip) 20 hr and alpha-mehyl-para-tyrosine (AMPT; 200 mg/kg, ip), one hour before the experiment induced significant catalepsy in rats as assessed by bar test. There was a significant increase in the time spent on the bar in bar test as compared to the control untreated rats. L-dopa (100 mg/kg, ip) and carbidopa (10 mg/kg, ip) combination, a conventional therapy was less effective in reversing reserpine-induced catalepsy. Pretreatment with FK506, a neuroprotectant (0.5-2 mg/kg, po) not only dose dependently reduced the catalepsy in reserpine-treated rats but a lower dose (1 mg/kg) potentiated the motor stimulant actions of sub threshold dose of L-dopa (100 mg/kg, ip) and carbidopa (10 mg/kg, ip) combination. Anticataleptic effect of FK506 was blocked dose dependently by specific D2 receptor blocker sulpiride (25-100 mg/kg, ip). In conclusion, the findings of the present study suggest that FK506 has an indirect modulatory action on the dopamine D2 receptors. FK506 being a neuroprotectant, could be used as an effective adjunct to L-dopa for the treatment of neuroleptic-induced extrapyramidal side effects.

Role of antioxidants in chronic fatigue syndrome in mice.

The present study was carried out using mice model of chronic fatigue syndrome (CFS) in which mice were forced to swim everyday for 7 days for a 6 min session. There was a significant increase in despair behavior (immobility period) in saline treated mice on successive days. Treatment with potent antioxidants carvedilol (5 mg/kg, i.p.) and melatonin (10 mg/kg, i.p.) produced a significant reduction in immobility period. Similar results were observed with herbal products St. John's Wort (Hypericum perforatum L) (10 mg/kg, p.o.) and GS-02 (20 mg/kg, p.o.). Fluoxetine, a selective serotonin reuptake inhibitor produced a significant effect only on first and second day of its treatment. Biochemical analysis revealed that chronic swim test significantly increased lipid peroxidation and catalase levels in whole brains of mice. There was a decrease in the levels of super oxide dismutase (SOD) and glutathione reductase (GSH) in the brain. Administration of carvedilol, melatonin, GS-02 and St. John's Wort restored the levels of lipid peroxidation and glutathione. The enzymes SOD and catalase were also restored. Fluoxetine affected the biochemical variables not to the same extent as other treatments. The findings of the present study suggest that oxidative stress might play a significant role in the pathophysiology of CFS. Thus antioxidants and herbal products like St. Johns wort and GS-02 could be useful in the treatment of CFS.

Role of adenosine in drug-induced catatonia in mice.

Parkinson's disease is one of the most common neurodegenerative disorders affecting large majority of population who are older than age of 65. Apart from dopamine, acetylcholine and glutamate, adenosinc has also been identified in the basal ganglia. Adenosine modulates the release of a variety of neurotransmitters including dopamine. In order to establish adenosine-dopamine interactions in drug-induced catatonia we studied the effect of adenosine in drug-induced catatonia in mice. In the present study adenosine dose dependently produced catatonia when assessed on rota-rod and bar tests in mice. Adenosine also potentiated the catatonic effect of perphenazine. L-dopa plus carbidopa or OR-486 (a potent centrally acting COMT inhibitor) completely reversed adenosine-induced catatonia. Since reversal by scopolamine of adenosine-induced catatonia was not to the same extent as with l-dopa and OR-486 it appears that catecholamines particularly dopamine rather than cholinergic modulation is more important in adenosine induced catatonia. The motor dysfunction (catatonia) could be easily assessed using rota-rod test apparatus in mice.