Substantia nigra lesions attenuate the development of hypertension and behavioural hyperreactivity in spontaneously hypertensive rats

The possible relation between changes in behaviour and the development of hypertension was investigated. Depletion of striatal dopamine by lesions in the substantia nigra of Spontaneously Hypertensive Rats (SHR) was associated with an inhibition of the development of hypertension. In the open field a decrease in rearing score was found with no effect on other parameters. Rearing activity was significantly correlated with blood pressure as well as with striatal dopamine content. Blood pressure was weakly, although significantly, correlated with striatal dopamine content. Neither blood pressure nor striatal dopamine content was significantly correlated with ambulation activity. In normotensive Wistar-Kyoto rats a decrease was also found in rearing activity after nigra lesions, although this effect was less pronounced. Antihypertensive treatment of SHR with captopril or hydralazine did neither affect striatal dopamine levels nor open-field behaviour. Induction of renal hypertension or DOCA-salt hypertension in Wistar rats did not influence brain dopamine or behaviour. The results support the suggestion that brain dopamine systems may play a role in the development of hypertension in SHR as well as in the changes in behaviour observed in these rats. Changes in behaviour do not appear to be mediated by changes in blood pressure per se.     

Effect of the anxiolytic drug buspirone on prolactin and corticosterone secretion in stressed and unstressed rats

Buspirone is an atypical anxiolytic drug that exerts its action at a receptor site other than the GABA-benzodiazepine-chloride ionophore complex. The present study examined the effect of buspirone on plasma prolactin and corticosterone levels in both control and stressed rats. In unstressed rats, buspirone produced dose-dependent increases in plasma prolactin and corticosterone levels. The minimal doses of buspirone which led to significant elevations in plasma prolactin and corticosterone levels were 1.0 and 2.0 mg/kg (IP), respectively. The effect of buspirone on both hormones was maximal 30 minutes after injection. The plasma levels of prolactin and corticosterone were significantly elevated in rats that were stressed using a conditioned fear paradigm. Buspirone produced a dose-dependent attenuation of the stress-induced increase in prolactin secretion. The stress-induced increase in corticosterone secretion was inhibited by the 0.5 mg/kg (IP) dose but not by the 2.0 mg/kg (IP) dose of buspirone, which increased corticosterone secretion both in stressed and unstressed rats. These data suggest that the effect of buspirone on plasma prolactin and corticosterone levels may be mediated by two different mechanisms of action.     

Glucocorticoid inhibition of fibroblast contraction of collagen gels

When skin fibroblasts are grown in culture on collagen gels, the collagen gels contract. We have studied the effects of various steroids on the contraction process. Cortisol, beta-estradiol and dexamethasone inhibited fibroblast-mediated gel contraction at low (10(-8) to 10(-9) M) concentrations whereas dihydrotestosterone was without effect. These effects were time and concentration dependent and could be reversed if the steroids were removed. This system may be useful for assaying the activities of various steroids in terms of their activities and modulating effects on connective tissue.     

Early SARS-CoV-2 Reinfections within 60 Days and Implications for Retesting Policies

Illustrated by a clinical case supplemented by epidemiologic data, early reinfections with SARS-CoV-2 Omicron BA.1 after infection with Delta variant, and reinfection with Omicron BA.2 after Omicron BA.1 infection, can occur within 60 days, especially in young, unvaccinated persons. The case definition of reinfection, which influences retesting policies, should be reconsidered.     

Effect of melatonin on sleep, behavior, and cognition in ADHD and chronic sleep-onset insomnia

OBJECTIVE: To investigate the effect of melatonin treatment on sleep, behavior, cognition, and quality of life in children with attention-deficit/hyperactivity disorder (ADHD) and chronic sleep onset insomnia. METHOD: A total of 105 medication-free children, ages 6 to 12 years, with rigorously diagnosed ADHD and chronic sleep onset insomnia participated in a randomized, double-blind, placebo-controlled trial using 3 or 6 mg melatonin (depending on body weight), or placebo for 4 weeks. Primary outcome parameters were actigraphy-derived sleep onset, total time asleep, and salivary dim light melatonin onset. RESULTS: Sleep onset advanced by 26.9 +/- 47.8 minutes with melatonin and delayed by 10.5 +/- 37.4 minutes with placebo (p < .0001). There was an advance in dim light melatonin onset of 44.4 +/- 67.9 minutes in melatonin and a delay of 12.8 +/- 60.0 minutes in placebo (p < .0001). Total time asleep increased with melatonin (19.8 +/- 61.9 minutes) as compared to placebo (-13.6 +/- 50.6 minutes; p = .01). There was no significant effect on behavior, cognition, and quality of life, and significant adverse events did not occur. CONCLUSION: Melatonin advanced circadian rhythms of sleep-wake and endogenous melatonin and enhanced total time asleep in children with ADHD and chronic sleep onset insomnia; however, no effect was found on problem behavior, cognitive performance, or quality of life.     

Diagnostic hallmarks and pitfalls in late-onset progressive transthyretin-related amyloid-neuropathy

Familial amyloid polyneuropathy (FAP) is a progressive systemic autosomal dominant disease caused by pathogenic mutations in the transthyretin (TTR) gene. We studied clinical, electrophysiological, histopathological, and genetic characteristics in 15 (13 late-onset and two early-onset) patients belonging to 14 families with polyneuropathy and mutations in TTR. In comparison, we analysed the features of nine unrelated patients with an idiopathic polyneuropathy, in whom TTR mutations have been excluded. Disease occurrence was familial in 36 % of the patients with TTR-associated polyneuropathy and the late-onset type was observed in 86 % (mean age at onset 65.5 years). Clinically, all late-onset TTR-mutant patients presented with distal weakness, pansensory loss, absence of deep tendon reflexes, and sensorimotor hand involvement. Afferent-ataxic gait was present in 92 % leading to wheelchair dependence in 60 % after a mean duration of 4.6 years. Autonomic involvement was observed in 60 %, and ankle edema in 92 %. The sensorimotor polyneuropathy was from an axonal type in 82 %, demyelinating or mixed type in 9 % each. Compared to the TTR-unmutated idiopathic polyneuropathy patients, we identified rapid progression, early ambulatory loss, and autonomic disturbances, associated with a severe polyneuropathy as red flags for TTR–FAP. In 18 % of the late-onset TTR-FAP patients, no amyloid was found in nerve biopsies. Further diagnostic pitfalls were unspecific electrophysiology, and coincident diabetes mellitus (23 %) or monoclonal gammopathy (7 %). We conclude that a rapid disease course, severely ataxic gait, hand involvement, and autonomic dysfunction are diagnostic hallmarks of late-onset TTR–FAP. Genetic analysis should be performed even when amyloid deposits are lacking or when polyneuropathy-causing comorbidities are concomitant.     

Prognosis of ischemic colitis: comparison of color doppler sonography with early clinical and laboratory findings

OBJECTIVE. The objective of this study was to compare the value of color Doppler sonography with early clinical and laboratory findings in determining the prognosis of patients with ischemic colitis. SUBJECTS AND METHODS. We reviewed the early clinical, laboratory, and color Doppler sonographic data of 24 patients with ischemic colitis. The patients were divided into two groups on the basis of their outcome. The first group comprised the patients with transient ischemia who recovered uneventfully, and the second group included the patients who needed surgery because of symptomatic transmural colic gangrene or colic stricture. Clinical data and laboratory values were compared with color Doppler sonographic findings including colic wall thickness, presence of stratification, and arterial flow in the bowel wall. RESULTS. At univariate analysis, increased age (p = 0.007), leukocyte count (p = 0.030), lactate dehydrogenase level (p = 0.030), blood lactate level (p = 0.041), and absence of vascular flow in the colic wall (p<0.001) were significantly related to complicated ischemic colitis. At multivariate analysis, absence of arterial flow was the only significant predictor of complicated ischemic colitis (p = 0.002), with a sensitivity of 82%, a specificity of 92%, a positive predictive value of 90%, and a negative predictive value of 86%. CONCLUSION. Absence of arterial flow in the wall of the ischemic colon on initial color Doppler sonography is suggestive of an unfavorable outcome and is more closely associated with outcome than early clinical and laboratory findings.     

Assessment of hepatic perfusion parameters with dynamic MRI.

Quantification of hepatic perfusion parameters greatly contributes to the assessment of liver function. The purpose of this study was to describe and validate the use of dynamic MRI for the noninvasive assessment of hepatic perfusion parameters. The signal from a fast T(1)-weighted spoiled gradient-echo sequence preceded by a nonslice-selective 90 degrees pulse and a spoiler gradient was calibrated in vitro with tubes filled with various gadolinium concentrations. Dynamic images of the liver were obtained after intravenous bolus administration of 0.05 mmol/kg of Gd-DOTA in rabbits with normal liver function. Hepatic, aortic, and portal venous signal intensities were converted to Gd-DOTA concentrations according to the in vitro calibration curve and fitted with a dual-input one-compartmental model. With MRI, hepatic blood flow was 100 +/- 35 mL min(-1) 100 mL(-1), the arterial fraction 24 +/- 11%, the distribution volume 13.0 +/- 3.7%, and the mean transit time 8.9 +/- 4.1 sec. A linear relationship was observed between perfusion values obtained with MRI and with radiolabeled microspheres (r = 0.93 for hepatic blood flow [P < 0.001], r = 0.79 for arterial blood flow [P = 0.01], and r = 0.91 for portal blood flow [P < 0.001]). Our results indicate that hepatic perfusion parameters can be assessed with dynamic MRI and compartmental modeling.     

Positron emission tomography and single photon emission computed tomography in epilepsy care

Radiopharmaceutical brain imaging is clinically applied in planning resective epilepsy surgery. Cerebral sites of seizure generation-propagation are highly associated with regions of hyperperfusion during seizures, and with glucose hypometabolism interictally. For surgical planning in epilepsy, the functional imaging modalities currently established are ictal single photon emission computed tomography (SPECT) with [(99m)Tc]technetium-hexamethylpropyleneamine oxime (HMPAO) or with [(99m)Tc]technetium-ethylene cysteine dimer (ECD), and interictal positron emission tomography (PET) with 2-[(18)F]fluoro-2-deoxyglucose (FDG). Ictal SPECT and interictal FDG PET can be used in presurgical epilepsy evaluations to reliably: (1) determine the side of anterior temporal lobectomy, and in children the area of multilobar resection, without intracranial electroencephalographic recording of seizures; (2) select high-probability sites of intracranial electrode placement for recording ictal onsets; and, (3) determine the prognosis for complete seizure control following anterior temporal lobe resection. Coregistration of a patient's structural (magnetic resonance) and functional images, and statistical comparison of a patient's data with a normal data set, can increase the sensitivity and specificity of these SPECT and PET applications to the presurgical evaluation.