Decreased CSF pH at ventral brain stem induces widespread c-Fos immunoreactivity in rat brain neurons.

Physiological evidence has indicated that central respiratory chemosensitivity may be ascribed to neurons located at the ventral medullary surface (VMS); however, in recent years, multiple sites have been proposed. Because c-Fos immunoreactivity is presumed to identify primary cells as well as second- and third-order cells that are activated by a particular stimulus, we hypothesized that activation of VMS cells using a known adequate respiratory stimulus, H(+), would induce production of c-Fos in cells that participate in the central pH-sensitive respiratory chemoreflex loop. In this study, stimulation of rostral and caudal VMS respiratory chemosensitive sites in chloralose-urethane-anesthetized rats with acidic (pH 7.2) mock cerebrospinal fluid induced c-Fos protein immunoreactivity in widespread brain sites, such as VMS, ventral pontine surface, retrotrapezoid, medial and lateral parabrachial, lateral reticular nuclei, cranial nerves VII and X nuclei, A(1) and C(1) areas, area postrema, locus coeruleus, and paragigantocellular nuclei. At the hypothalamus, the c-Fos reaction product was seen in the dorsomedial, lateral hypothalamic, supraoptic, and periventricular nuclei. These results suggest that 1) multiple c-Fos-positive brain stem and hypothalamic structures may represent part of a neuronal network responsive to cerebrospinal fluid pH changes at the VMS, and 2) VMS pH-sensitive neurons project to widespread regions in the brain stem and hypothalamus that include respiratory and cardiovascular control sites.     

The investigation of the combined effects of gamma irradiation and environmental manipulation on mortality and sterility of Rhyzopertha dominica (Fabricius) (Coleoptera: Bostrichidae)

With respect to the limitations use of methyl bromide and phosphine, employing ionizing radiation to control stored product pests has attracted great attention. The aim of this study is the investigation of the combined effects of gamma irradiation as viable alternatives to synthetic insecticides and environmental management on mortality and sterility of Rhyzopertha dominica (Fabricius) in a wheat cultivar (Gascogen). The effect of doses range from 30 to 2000?Gy gamma irradiation in combination with manipulation of temperature (15, 21, 27 and 32?°C) and relative humidity (20%, 50%, 65% and 85%) on 5–10?days old adults of R. dominica in Gascogen cultivar of wheat were explored. The experiments were repeated three times and conducted in The Nuclear Agriculture Research School in Karaj and laboratory of shahid steki silo in shahre-kord. Probit analysis revealed that both temperature and relative humidity had combined effects when used with gamma irradiation. The lowest doses of gamma ray required to kill 25% (14.2?Gy) and 50% (610.8?Gy) of the population (LD₂₅ and LD₅₀) were recorded at 21?°C and 85% relative humidity respectively. The low dose for 99% mortality (LD₉₉; 2386.7?Gy) was recorded for beetles maintained at 21?°C and 50% relative humidity. The effect of temperature (15, 21, 27 and 32?°C) on sterility caused by gamma irradiation was also investigated. The results showed that the F₁ generation emerged only when the beetles were treated with doses of 0–100?Gy at 32?°C and 0–70?Gy at 27?°C. These results indicate that temperature and relative humidity play an important role in the susceptibility of the lesser grain beetle to gamma irradiation. The results suggest that controlling the efficiency of gamma radiation through environmental control allows the use of low doses of gamma radiation that have a less harmful effect on human health, non-target organisms and seed agronomic features.     

Ca2+ antagonists and db-cAMP sustain a rise in renal blood flow induced by acetylcholine in indomethacin-treated dogs

Renal arterial infusion of acetylcholine (ACh) in the dog normally produces a sustained rise in sodium excretion (UNaV) and in renal plasma flow (RPF). When prostaglandin (PG) synthesis is inhibited, ACh induces only a transient increase in UNaV and RPF followed by a progressive decline in UNaV and RPF, and a rise in renin secretory rate (RSR). Renal arterial infusion of PGE2 but not a vasodilator such as bradykinin restored the response to ACh to normal in indomethacin (Indo)-treated dogs. During renal arterial infusion of dibutyryl cyclic AMP (6 mg/min), ACh also produced a sustained increase in UNaV and RPF despite an inhibition of PG synthesis by Indo. Renal arterial infusion of verapamil (60 micrograms/min) or diltiazem (60 micrograms/min) also prevented the subsequent fall in RPF when ACh was infused; RSR, however, did not show a rise. The results suggest that synthesis of PGE2 with stimulation of cAMP is required for sustained ACh action. When PGE synthesis is inhibited, ACh may produce renal vasoconstriction by increasing intracellular Ca2+ concentration. The partial effect of calcium channel blockers suggests that release of calcium from intracellular stores as well as calcium entry may mediate the response.     

Comparison of outcomes of percutaneous coronary intervention on proximal versus non-proximal left anterior descending coronary artery, proximal left circumflex, and proximal right coronary artery: A cross-sectional study

Background

There have been few prospective studies examining the utility of routine exercise treadmill testing (ETT) early after percutaneous coronary intervention (PCI). The objective of this study was to examine the impact of a routine ETT strategy early after PCI on follow-up cardiac events and procedures.

Methods

We examined 136 patients who underwent routine ETT at 6 weeks post-PCI in the ADORE trial. The ETT was classified as positive, indeterminate, or negative. The Duke Treadmill Score (DTS) was calculated for all patients. Follow-up occurred at 9 months.

Results

ETT results at 6 weeks were: 32 (23.5%) positive, 24 (17.6%) indeterminate and 80 (58.8%) negative. At 9 months, the composite event rate was 21.9% in those with a positive ETT, 20.8% in those with an indeterminate ETT and 12.5% in those with a negative ETT (p = 0.25 positive vs. negative ETT). The sensitivity of early ETT for predicting clinical events was 41.2%, the specificity was 73.3%, the positive predictive value was 21.9% and the negative predictive value was 87.5%. At 9 months, the cardiac procedure rate was 18.8% in those with a positive test, 13.0% in those with an indeterminate test, and 6.3% in those with a negative test (p = 0.07 positive vs. negative ETT). In a multivariate logistic regression model, coronary stenting during PCI and a ≥ 85% MPHR achieved were found to be inversely associated with clinical events. However, the DTS did not independently predict clinical events.

Conclusion

Although the statistical power of the study was limited by the small number of clinical events (particularly MI and death), the results of this study support the ACC/AHA guidelines that exercise treadmill testing should not be used routinely after PCI.     

Design,Synthesis, Molecular Docking,and Molecular Dynamics Simulation Studies of Novel 3-Hydroxypyridine-4-one Derivatives as Potential Acetylcholinesterase Inhibitors

Researchers have focused on inhibiting acetylcholinesterase for Alzheimer's disease treatment. In this study, some novel AChE inhibitors were synthesized using hydroxypyridin-4-one plus benzylpiperidine scaffolds which were evaluated using Ellman's method. Accordingly, ((1-(4-methoxyphenethyl)piperidin-4-yl)amino)methyl)-5-hydroxy-1-methylpyridin-4(1H)-one (VII_d) showed weaker but promising AChE inhibition compared to donepezil (IC₅₀=143.090 nM). The average RMSD values of VII_d was found to be 2.25 indicated less structural changes in the active site residues. The phenyl group of the phenyl-ethyl-N-piperidine moiety of VII_d formed hydrophobic interactions with Trp285 and Tyr340. There was a π-cation interaction between nitrogen atom of piperidine ring and Phe294. Another π-cation interaction was found between type 2 amine of linker and Trp85. Piperidine ring interacted with Tyr336, Tyr123, and Phe337 through hydrophobic interactions. Indeed, the VII_d was predicted to be absorbed across the gastrointestinal tract, though it may be pumped out by P-gp. Indeed, VIId can permeate through the blood brain barrier. MD simulation studies revealed that benzyloxy moiety plays a role similar to benzylpiperidine moiety of donepezil in binding to the active site residues. Also, carbonyl group functioned similar to indanone ketone group. Overall; further research on VII_d may lead to introduction of a novel class of AChE inhibitors.     

Somatosensory evoked potential, neurological examination and magnetic resonance imaging for assessment of cervical spinal cord decompression

The present study was designed to determine the relationship between neurological testing, anatomical imaging, and electrophysiological monitoring for assessing outcome of cervical spinal cord decompression. We prospectively studied 28 consecutive patients (age 39-76 yr) who were subjected to presurgical-(1-3 wk) and postsurgical (3-4 mo) neurological examination and recording of the median nerve somatosensory evoked potential (SEP). In 13 patients, magnetic resonance imaging (MRI) was also performed. Changes in neurological function, SEP and MRI were evaluated and graded as (1) improvement,(2) no change or (3) deterioration. Neurological outcome (NO) was based on changes in motor grade strength, sensory, reflexes and gait. The SEP outcome was based on changes in latency and disappearance of SEP waveform components whereas MRI evaluation was based on changes in spinal cord and canal diameters. Significance of association between NO, SEP and MRI was determined by Pearson's Chi-Square statistic (P<.05). The SEP improved in 71% (20/28) and deteriorated in 28% (8/28) of the subjects. An association between SEP changes and NO was found in 82% (23/28) of the subjects (P = .0038). Decompression increased the spinal canal diameter in 92% (12/13), and the spinal cord diameter in 38% (5/13) of the subjects. An association between NO, or SEP and MRI was not detected. Changes in median nerve SEP latency appear to be predictive of the neurological status of patients subjected to cervical spinal cord decompression. Postoperative increments in SEP latency or disappearance of the SEP waves were indicative of poor outcome after surgical decompression of the cervical spinal cord.     

Synergism between cocaine and atropine at the caudal ventrolateral medulla of cats

We have previously reported that the anticholinergic properties of cocaine may be important in cocaine induced apneusis. We have studied the effects of the cholinergic muscarinic antagonist atropine (ATR) on cocaine induced apneusis at the caudal chemosensitive areas of the ventrolateral medulla oblongata (CVLM). Experiments were performed in urethane anesthetized and tracheotomized cats with the CVLM surgically exposed. Topical application of ATR (44 mM ) to the CVLM produced significant decrements in minute ventilation (V(E)) and mean arterial blood pressure (MABP) (P<0.05) but the effects on tidal volume (V(T)), respiratory frequency (f) and heart rate (HR) were not significant. Administration of cocaine (37 mM) to ATR pretreated animals increased the incidence of cocaine induced respiratory arrest to more than twofold greater than when cocaine was administered in the absence of pretreatment. The ATR pretreated animals that did not experience inspiratory arrest after cocaine were shown to exhibit significant decrements in f and V(E) as a consequence of prolonged inspiratory pauses. The reduction in MABP after cocaine in ATR pretreated animals was also significant. These results suggest that ATR enhances the central respiratory toxicity of cocaine by acting synergistically at CVLM chemosensitive sites.