Pharmacological treatments for acute migraine: quantitative systematic review

Endometriosis and urinary calculosis can co-occur. Clinical studies have shown that both painful and non-painful endometriosis in women are associated with enhanced pain and referred muscle hyperalgesia from urinary calculosis, but the mechanisms underlying this phenomenon are still poorly understood. The aim of this study was to develop an animal model adequate to explore this viscero-visceral interaction in standardized conditions.Using a model of endometriosis previously developed to study reduced fertility and vaginal hyperalgesia, endometriosis (endo) or sham-endometriosis (sham-endo) was induced in rats by autotransplantation of small pieces of uterus (or, for sham-endo, fat) on cascade mesenteric arteries, ovary, and abdominal wall. After the endometrial, but not the fat autografts had produced fluid-filled cysts (3 weeks), urinary calculosis was induced by implanting an artificial stone into one ureter. Pain behaviors were monitored by continuous 24-h videotape recordings before and after stone implantation. Referred muscle hyperalgesia was assessed by measuring vocalization thresholds to electrical stimulation of the oblique musculature (L1 dermatome). The data were compared with previously reported data from rats that had received only the stone. Neither endo nor sham-endo alone induced pain behaviors. Following stone implantation, in endo rats compared to sham-endo and stone-only rats, pain behaviors specifically associated with urinary calculosis were significantly increased and new pain behaviors specifically associated with uterine pathology became evident. Muscle hyperalgesia was also significantly increased. To explore the relationship between the amount of endometriosis and that of ureteral pain behavior, two separate groups of endo rats were treated with either a standard non-steroidal anti-inflammatory drugs (ketoprofen) or placebo from the 12th to the 18th day after endometriosis induction. The stone was implanted on the 21st day. Ketoprofen treatment compared to placebo significantly reduced the size of the cysts and both ureteral and uterine pain behaviors post-stone implantation. The size of the cysts showed a significant linear correlation with the post-stone ureteral pain behaviors. In conclusion, endo increased pain crises and muscle hyperalgesia typically induced by a ureteral calculosis, and the ureteral calculosis revealed additional pain behaviors typically induced by uterine pathophysiology; and this enhancement was a function of the degree of endometriosis. This result closely reproduces the condition observed in humans and could be due to a phenomenon of 'viscero-visceral' hyperalgesia, in which increased input from the cyst implantation sites to common spinal cord segments (T10-L1) facilitates the central effect of input from the urinary tract.     

CYP2A5-mediated activation and early ultrastructural changes in the olfactory mucosa: studies on 2,6-dichlorophenyl methylsulfone.

2,6-Dichlorophenyl methylsulfone (2,6-diClPh-MeSO2) is a potent olfactory toxicant reported to induce endoplasmic reticulum (ER) stress, caspase activation, and extensive cell death in mice. The aim of the present study was to examine cytochrome P450 (P450)-dependent bioactivation, nonprotein sulfhydryl (NP-SH) levels, and early ultrastructural changes in mouse olfactory mucosa following an i.p. injection of 2,6-diClPh-MeSO2 (32 mg/kg). A high covalent binding of 2,6-diClPh-14C-MeSO2 in olfactory mucosa S9 fraction was observed, and the CYP2A5/CYP2G1 substrates coumarin and dichlobenil significantly decreased the binding, whereas the CYP2E1 substrate chlorzoxazone had no effects. An increased bioactivation was detected in liver microsomes of mice pretreated with pyrazole, known to induce CYP2A4, 2A5, 2E1, and 2J, and addition of chlorzoxazone reduced this binding. 2,6-DiClPh-14C-MeSO2 showed a marked covalent binding to microsomes of recombinant yeast cells expressing mouse CYP2A5 or human CYP2A6 compared with wild type. One and 4 h after a single injection of 2,6-diClPh-MeSO2, the NP-SH levels in the olfactory mucosa were significantly reduced compared with control, whereas there was no change in the liver. Ultrastructural studies revealed that ER, mitochondria, and secretory granules in nonneuronal cells were early targets 1 h after injection. We propose that lesions induced by 2,6-diClPh-MeSO2 in the mouse olfactory mucosa were initiated by a P450-mediated bioactivation in the Bowman's glands and depletion of NP-SH levels, leading to disruption of ion homeostasis, organelle swelling, and cell death. The high expression of CYP2A5 in the olfactory mucosa is suggested to play a key role for the tissue-specific toxicity induced by 2,6-diClPh-MeSO2.     

Sonographic examination of the oral phase of swallowing: bolus image enhancement

PURPOSE: The purpose of this study was to evaluate the ability of 4 liquid boluses to enhance pixel brightness and the ease with which the boluses could be identified during the sonographic evaluation of oral swallowing in healthy young adults. METHODS: Ten healthy adult volunteers (5 men and 5 women), ranging in age from 21 to 31 years, underwent sonographic evaluation of the oral phase of swallowing while sitting in their usual feeding position. We compared the ability of the 4 following liquids to improve sonographic visualization of swallowing with that of water: a carbonated cola beverage, 5.0 ml of Thick-It in 120 ml of water, 2.5 ml of Thick-It in 120 ml of water, and 7.5 ml of confectioners' sugar in 120 ml of water. Water was used as a control. In each case, 5 ml of the liquid was introduced into the subject's oral cavity using a syringe, and the subject was instructed to swallow. Digitized still images and recorded video sequences of sonographic examinations of the swallowing were analyzed. The brightness of the bolus image on selected digitized video frames was measured digitally using Image Analyst software. Pixel brightness within selected regions of interest for each of the test liquids was statistically compared with that for water. Seven clinicians rated the visualization of each test liquid and water on paired sonographic videotape sequences. These ratings and the level of agreement between them were statistically tested. RESULTS: Only the carbonated cola beverage demonstrated statistically greater pixel brightness than that of water on digitized video frames (p = 0.01), whereas both cola (with a moderate inter-rater agreement, kappa = 0.50) and 5.0 ml Thick-It mixed with 120 ml of water (with a fair inter-rater agreement, kappa = 0.24) were significantly better visualized on sonographic video sequences. CONCLUSIONS: The digital still-frame analysis confirmed the clinicians' ratings of bolus visualization on real-time sonography, but dynamic sonography is more important than still frames in assessing sonographic swallow media because the dynamic images more closely parallel what is seen in clinical practice. Future investigations of sonographic contrast agents for use in the examination of the oral phase of swallowing should use both static digital (still-frame) and dynamic (real-time) assessment methods, as well as expert reviewers.     

Modified programme of in-patient (phase I) cardiac rehabilitation after acute myocardial infarction

A group of 61 men who suffered from myocardial infarction (MI) were divided into two groups: group A (31 patients post MI, one day at intensive care unit (ICU), no beta-blockers, physical therapy according to a seven-day programme) and group B (30 patients post MI, two days at ICU, with beta-blockers, physical therapy according to a seven-day programme). Results from both groups were compared with a control group (C) (38 patients post MI, three days at ICU, physical therapy according to a longer ten-day graded programme). The objective of this study was to assess the efficacy of a proposed modified rehabilitation programme in patients after acute MI on the basis of a submaximal stress test performed on a cycle ergometer and to find out which stress test parameters might be used for the selection of an appropriate phase 2 rehabilitation programme. The performed analysis of correlation between exercise and resting parameters showed statistical relevancy with regard to systolic blood pressure in group A. Maximal load (WATs), metabolic cost (METs), maximal heart rate (beats/min), stress-test time (T-test) and time of normalization for the exercise parameters (t(n)) are the parameters of the stress test that should be taken into consideration for appropriate selection of an out-patient (phase 2) rehabilitation programme.     

Near-infrared spectroscopy in the detection of regional tissue oxygenation during hypoxic events in preterm infants undergoing critical care.

OBJECTIVES: To determine whether pulse oximetry-detected episodes of desaturation are associated with impairment of cerebral and somatic (renal) tissue oxygenation in mechanically ventilated preterm neonates. DESIGN: Observational cross-sectional study. SETTING: Neonatal intensive care unit of a university-affiliated children's hospital. PATIENTS: Ten mechanically ventilated preterm (gestational age 24-32 wks) infants. INTERVENTIONS: In addition to the traditional monitoring of hemodynamic variables that included pulse oximetry (Sao2), near-infrared spectroscopy (NIRS) was used to evaluate the cerebral and somatic (renal) tissue oxygen saturation (rSO2C and rSO2R, respectively). MEASUREMENTS AND MAIN RESULTS: A total of 40 rSO2C and rSO2R measurements were simultaneously recorded: 20 during hypoxic events when the Sao2 was /=4 secs (cases) and generally ranged between 70% and 80%, and 20 measurements when the Sao2 was >/=85% (paired controls). Additionally, the fractional oxygen extraction (FOE) from the cerebral (FOEC) and renal (FOER) tissue was calculated. All the measurements were made under steady conditions during a 2-hr period. The rSO2C, rSO2R, FOEC, and FOER among the cases (Sao2 /= 85%) were compared using the paired Student's t-test. Both rSO2C and rSO2R during the desaturation episodes were lower than in the controls (51.6 +/- 6.3% vs. 66.2 +/- 10.2%, p < .0001 and 61.1 +/- 6.8% vs. 80.1 +/- 10.0%, p < .0001, respectively). The FOEC during the hypoxic episodes was comparable with control levels but increased in renal tissue. However, during two of the desaturation episodes (10%), the rSO2C and FOEC levels (which were <44% and >0.47, respectively) may reflect compromised tissue oxygen supply. CONCLUSIONS: In the majority of mechanically ventilated preterm neonates, the reduction in cerebral and renal tissue oxygenation associated with short periods of decreased arterial saturation to 70-80% does not significantly compromise oxygen utilization in the cerebral tissue but increases oxygen extraction in the renal tissue, which might cause ischemic tissue injury following a further reduction in oxygen delivery.