Expression of type 2 nitric oxide synthase and p21 in oral squamous cell carcinoma.

Nitric oxide (NO) has a complex role in tumour biology. Most cancer research has focused on the enzyme nitric oxide synthase-2 (NOS2), an inducible isoform responsible for prolonged NO production. In normal cells exposed to high NO concentrations, the tumour-suppressor gene, p53, promotes apoptosis via the p21 pathway, in an attempt to safeguard against potential NO-mediated DNA damage. In cancer cells with mutant p53, this pathway is unlikely to occur directly, although, p53-independent p21 expression and subsequent apoptosis can occur at higher NO concentrations. In this study, the possible direct association between NOS2 and p21 was assessed in oral squamous cell carcinoma. Immunohistochemistry was performed for NOS2 and p21 on 56 cases, and NOS2 activity was determined with citrulline assays in selected cases. A significant relationship was demonstrated between the immunohistochemical expression of NOS2 and its activity (P<0.001), but not between NOS2 and p21 expression (P=0.76). It is unlikely that the NO concentrations found in oral cancer (up to 10.3 pmol NO min(-1) mg protein(-1)) are sufficient to cause direct (p53-independent) p21 accumulation and subsequent apoptosis. As with many other tumours, since NO production has a detrimental role, its pharmacological inhibition in oral cancer represents an exciting area for possible future therapeutic manipulation.

Expression of nitric oxide synthase-2 in cutaneous squamous cell carcinoma of the head and neck.

Nitric oxide (NO) has a pivotal role in angiogenesis. The expression of NO synthase (NOS2) is down-regulated in basal cell skin cancer but we know of no studies that have investigated its expression in the more aggressive squamous cell skin carcinoma. This immunohistochemical study assessed NOS2 expression in 37 cases of head and neck squamous cell skin carcinoma. NOS2 expression was located in cells of the basal cell layer of epidermis, but was significantly increased in tumour epithelium. No correlations were found between NOS2 expression and tumour size or degree of tumour differentiation. The raised NO concentrations in these tumours may provide one explanation for their more aggressive behaviour than that of the slower-growing basal cell carcinoma.

Responses to hypercarbia induced by acetazolamide in panic disorder patients.

CO2 inhalation has been reported to induce panic attacks in panic disorder patients. State anxiety, somatic symptoms of anxiety, physiological changes, and cerebral blood flow (CBF) were monitored in panic disorder patients before and after intravenous injections of 1 g of acetazolamide (13 patients) and saline (10 patients), given under double-blind conditions. In spite of significant hypercarbia, as evidenced by increased CBF in the former group, only one subject reported panic and even that attack did not meet DSM-III-R criteria. There was only one significant difference between the drug and placebo groups; the acetazolamide group experienced significantly more dizziness.

Regional cerebral blood flow changes associated with amyl nitrite inhalation.

Regional cerebral blood flow (CBF), mood states and somatic symptoms were measured before and after inhalation of amyl nitrite in 10 physically healthy volunteers with a prior history of using volatile nitrites for recreational purposes. CBF was measured with the same technique, under identical laboratory conditions, in an equal number of normal volunteers. During CBF measurements, blood pressure, pulse rate, respiratory rate and end-tidal levels of carbon dioxide were monitored. The amyl nitrite group and the control group were compared on CBF, rating scale scores and physiological indices via analysis of variance. Amyl nitrite inhalation was associated with significant global increases in CBF, while the control group did not show any change. Pulse rate increase was the only physiological change associated with administration of the drug. Subjects who received the drug reported significant decrease in anger, fatigue and depression and increased palpitation, breathing difficulty, dizziness and headache. Changes in the rating scale scores, physiological indices, and somatic symptoms after amyl nitrite did not correlate with regional CBF change.

Acute changes in cerebral blood flow associated with marijuana smoking.

Cerebral blood flow (CBF) was measured in experienced (ES) and inexperienced (IS) marijuana smokers with the 133xenon inhalation technique before and after smoking both a high-potency marijuana cigarette and a placebo marijuana cigarette. CBF was measured twice under resting conditions in a control group. Mood states before and after marijuana smoking were quantified with the Profile of Mood States (POMS). Analyses of POMS factors after smoking marijuana revealed IS had an increase in anxiety while ES had a decrease. IS also had a significant increase in depression and decrease in vigor, but neither variable changed in the ES. After marijuana, CBF decreased in IS, but in ES, it increased in comparison with the 2 control runs. In both IS and ES, CBF changes following placebo administration were similar to those associated with marijuana smoking. However, in IS, the marijuana-induced CBF decrease was significantly higher than that associated with placebo. There were no statistically significant differences between the CBF increase seen after placebo and marijuana in ES. Anxiety, anger, fatigue, confusion and depression had significant negative correlations with CBF while vigor correlated positively, but the anxiety factor was the only one to account for a significant percentage of the change (parital correlation) in hemispheric CBF.

Abnormal resting regional cerebral blood flow patterns and their correlates in schizophrenia.

Regional cerebral blood flow (CBF) was measured under resting conditions in 108 right-handed schizophrenic inpatients and a matched group of normal controls with the xenon 133 inhalation technique. Forty-six patients were free of all medication for two weeks. There were no significant differences in CBF to the two hemispheres. The patients showed a comparatively reduced anteroposterior (AP) gradient for CBF. Though there were no differences in frontal flow, the patients had higher flow to several postcentral brain regions, bilaterally. Cerebral blood flow in the patients correlated inversely with age and positively with carbon dioxide level. Women had higher flow than men. Duration of the illness was the only significant predictor of the reduced AP gradient in patients. Higher left temporal and right parietal flow were found to be the best discriminators between patients and controls. Mean hemispheric flow to both hemispheres and several brain regions correlated with the total score and the item, unusual thought content, of the Brief Psychiatric Rating Scale. There were no differences in regional CBF between medicated and unmedicated patients.

Determinants of resting regional cerebral blood flow in normal subjects.

Study of brain function via cerebral blood flow and metabolism measurements is believed to be of considerable significance in psychiatry. The present study examined the factors that determined patterns of regional cerebral blood flow (CBF) in 140 physically and mentally healthy, drug-free volunteers under resting conditions. Age, sex, and end-tidal CO2 levels were identified as the most powerful determinants of CBF, in that order. Age-related CBF reduction was found to be most marked in the frontal region. Women had higher CBF than men, and the difference was most obvious in the frontal region. The correlations between CO2 and CBF showed less striking, but significant, regional variations. Hematocrit was found to exert only minimal influence in the control of resting CBF.

Caffeine-induced cerebral blood flow changes in schizophrenia.

Cerebral blood flow (CBF) measurements and mental status examinations were performed before and 30 min after oral administration of 250 mg of caffeine or a placebo given under double-blind conditions, in two groups of patients with schizophrenia. Caffeine produced significant CBF reductions but no changes in the patient's clinical condition.