Regional Blood Flow in the Normal and Ischemic Brain Is Controlled by Arteriolar Smooth Muscle Cell Contractility and Not by Capillary Pericytes.

The precise regulation of cerebral blood flow is critical for normal brain function, and its disruption underlies many neuropathologies. The extent to which smooth muscle-covered arterioles or pericyte-covered capillaries control vasomotion during neurovascular coupling remains controversial. We found that capillary pericytes in mice and humans do not express smooth muscle actin and are morphologically and functionally distinct from adjacent precapillary smooth muscle cells (SMCs). Using optical imaging we investigated blood flow regulation at various sites on the vascular tree in living mice. Optogenetic, whisker stimulation, or cortical spreading depolarization caused microvascular diameter or flow changes in SMC but not pericyte-covered microvessels. During early stages of brain ischemia, transient SMC but not pericyte constrictions were a major cause of hypoperfusion leading to thrombosis and distal microvascular occlusions. Thus, capillary pericytes are not contractile, and regulation of cerebral blood flow in physiological and pathological conditions is mediated by arteriolar SMCs.

Angiophagy prevents early embolus washout but recanalizes microvessels through embolus extravasation.

Occlusion of the microvasculature by blood clots, atheromatous fragments, or circulating debris is a frequent phenomenon in most human organs. Emboli are cleared from the microvasculature by hemodynamic pressure and the fibrinolytic system. An alternative mechanism of clearance is angiophagy, in which emboli are engulfed by the endothelium and translocate through the microvascular wall. We report that endothelial lamellipodia surround emboli within hours of occlusion, markedly reducing hemodynamic washout and tissue plasminogen activator-mediated fibrinolysis in mice. Over the next few days, emboli are completely engulfed by the endothelium and extravasated into the perivascular space, leading to vessel recanalization and blood flow reestablishment. We find that this mechanism is not limited to the brain, as previously thought, but also occurs in the heart, retina, kidney, and lung. In the lung, emboli cross into the alveolar space where they are degraded by macrophages, whereas in the kidney, they enter the renal tubules, constituting potential routes for permanent removal of circulating debris. Retina photography and angiography in patients with embolic occlusions provide indirect evidence suggesting that angiophagy may also occur in humans. Thus, angiophagy appears to be a ubiquitous mechanism that could be a therapeutic target with broad implications in vascular occlusive disorders. Given its biphasic nature-initially causing embolus retention, and subsequently driving embolus extravasation-it is likely that different therapeutic strategies will be required during these distinct post-occlusion time windows.

A comparative study of efficacy of esmolol and fentanyl for pressure attenuation during laryngoscopy and endotracheal intubation.

OBJECTIVE: To compare the effectiveness of single bolus dose of esmolol or fentanyl in attenuating the hemodynamic responses during laryngoscopy and endotracheal intubation. METHODS: Ninety adult ASA I and ASA II patients were included in the study who underwent elective surgical procedures. Patients were divided into three groups. Group C (control) receiving 10 ml normal saline, group E (esmolol) receiving bolus dose of esmolol 2 mg/kg and group F (fentanyl) receiving bolus dose of fentanyl 2 µg/kg intravenously slowly. Study drug was injected 3 min before induction of anesthesia. Heart rate, systemic arterial pressure and ECG were recorded as baseline and after administration of study drug at intubation and 15 min thereafter. RESULTS: Reading of heart rate, blood pressure and rate pressure product were compared with baseline and among each group. The rise in heart rate was minimal in esmolol group and was highly significant. Also the rate pressure product at the time of intubation was minimal and was statistically significant rate 15 min thereafter in group E. CONCLUSION: Esmolol 2 mg/kg as a bolus done proved to be effective in attenuating rises in heart rate following laryngoscopy and intubation while the rise in blood pressure was suppressed but not abolished by bolus dose of esmolol.

Is premedication with midazolam more effective by the sublingual than the oral route?

BACKGROUND: In this study, we compared the sedative effects of sublingual midazolam solution with the oral tablet as premedication. Sixty pediatric patients of ASA physical status I and II were randomly selected to receive either 0.5 mg/kg of tablet or 0.5 mg/kg of sublingual solution of midazolam as premedication, about 45 min before elective surgery. MATERIALS AND METHODS: There were 30 patients in each group. In Group I, the patients received premedication in the form of oral midazolam tablet 0.5 mg/kg. In Group II, the patients received midazolam solution 0.5 mg/kg. The degree of sedation and ease of separation was assessed according to the Niall C. Wilton scale and the procedure of Davis Peter, respectively. The time for complete drug dissolution was noted in both the groups. Then, the patients were interviewed regarding their acceptance of taste. RESULTS: The sedation scores in the sublingual group were higher than in the oral group at 30 and 45 min after drug administration (P=0.0134 and P=0.0157). 66.6% of the patients in the sublingual group found it satisfactory as compared to 53.3% in the case of group receiving tablet. CONCLUSION: Thus, from the present study, it is concluded that premedication with midazolam is more effective by the sublingual than the oral route in children.

Analysis of protein expression regulated by the Helicobacter pylori ArsRS two-component signal transduction system.

Previous studies have shown that the Helicobacter pylori ArsRS two-component signal transduction system contributes to acid-responsive gene expression. To identify additional members of the ArsRS regulon and further investigate the regulatory role of the ArsRS system, we analyzed protein expression in wild-type and arsS null mutant strains. Numerous proteins were differentially expressed in an arsS mutant strain compared to a wild-type strain when the bacteria were cultured at pH 5.0 and also when they were cultured at pH 7.0. Genes encoding 14 of these proteins were directly regulated by the ArsRS system, based on observed binding of ArsR to the relevant promoter regions. The ArsRS-regulated proteins identified in this study contribute to acid resistance (urease and amidase), acetone metabolism (acetone carboxylase), resistance to oxidative stress (thioredoxin reductase), quorum sensing (Pfs), and several other functions. These results provide further definition of the ArsRS regulon and underscore the importance of the ArsRS system in regulating expression of H. pylori proteins during bacterial growth at both neutral pH and acidic pH.

A comparative study of intubating conditions of rocuronium bromide and suxamethonium in adult patients.

AIM: Intubating conditions after Suxamethonium, a time tested popular short acting depolarizing neuromuscular blocking agent, and Rocuronium, a recently introduced intermediate acting non depolarizing neuromuscular blocking agent, with Thiopentone as the sole induction agent, were compared in this study. MATERIALS AND METHODS: The patients were divided into two groups, each consisting of 30 patients: group a patient's received Rocuronium bromide, 0.6 mg/kg and group B patients received Suxamethonium chloride 1.5 mg/kg. In both the groups, jaw relaxation and vocal cord relaxation were considered for atraumatic laryngoscopy at 60 seconds or, if needed, at 75 seconds and then at 90 seconds. RESULTS: Intubation conditions were rated as excellent in 90% and good in 10% of the patients who received Rocuronium, and excellent in 100% of the patients who received Suxamethonium. CONCLUSION: It is concluded from this study that intubation can be performed under good to excellent conditions at 60-90 seconds after a bolus dose of Rocuronium of 0.6 mg/kg. The result of this study indicates that this new nondepolarizing neuromuscular blocking agent may be considered as a valuable alternative to Suxamethonium for rapid tracheal intubation, i.e., within 60 seconds, even after induction with Thiopentone as the sole anesthetic agent.

Addition of epidural Clonidine enhances postoperative analgesia: A double-blind study in total knee- replacement surgeries.

BACKGROUND: This study was undertaken to evaluate the analgesic effect of the combination of epidural Clonidine with Bupivacaine versus epidural Bupivacaine alone in patients undergone knee replacement surgery. MATERIALS AND METHODS: A randomized double-blind design was used, and 60 adult patients (40-60 years) of ASA grade I and II scheduled for post-operative pain relief in total knee replacement surgeries by epidural Clonidine were studied. Patients received either an epidural Clonidine (1µg/kg) with Bupivacaine (1.5mg/kg) group CL (n=30) or Bupivacaine alone group CT (n=30) for Knee replacement surgeries. The pain score, blood pressure, heart rate, respiratory rate were measured at fixed times during the first 24 h after operation. Onset and duration of sensory and motor blockade, duration of analgesia, and analgesic requirement were compared. RESULTS: The onset of sensory anesthesia was faster (493.8±31.66 in sec.) and the duration was significantly longer in Clonidine group (334.2 min). Requirement of supplementary analgesia (Inj. diclofenac) was markedly decreased in Clonidine group as evident from the findings that in control group 18 patients required 3 supplemental analgesic doses in first 24 hours as compared to only 3 patients in Clonidine group. Epidural Clonidine produced a significant decrease (P less than 0.05) in heart rate and blood pressure, whereas the respiratory rate was not affected. We also observed for side effects in both the groups. Incidence of significant hypotension was higher, 8 patients (26%) in Clonidine group compared to 2 patient (6%) in control group. Incidence of dryness of mouth was higher, 12 patients (48%) in Clonidine group compared to 5 (18%) in control group. CONCLUSION: The addition of Clonidine to Bupivacaine epiduraly prolongs motor and sensory block and analgesia, without an increased incidence of side effects.

Structural analysis of the DNA-binding domain of the Helicobacter pylori response regulator ArsR.

The Helicobacter pylori ArsS-ArsR two-component signal transduction system, comprised of a sensor histidine kinase (ArsS) and a response regulator (ArsR), allows the bacteria to regulate gene expression in response to acidic pH. We expressed and purified the full-length ArsR protein and the DNA-binding domain of ArsR (ArsR-DBD), and we analyzed the tertiary structure of the ArsR-DBD using solution nuclear magnetic resonance (NMR) methods. Both the full-length ArsR and the ArsR-DBD behaved as monomers in size exclusion chromatography experiments. The structure of ArsR-DBD consists of an N-terminal four-stranded beta-sheet, a helical core, and a C-terminal beta-hairpin. The overall tertiary fold of the ArsR-DBD is most closely related to DBD structures of the OmpR/PhoB subfamily of bacterial response regulators. However, the orientation of the N-terminal beta-sheet with respect to the rest of the DNA-binding domain is substantially different in ArsR compared with the orientation in related response regulators. Molecular modeling of an ArsR-DBD-DNA complex permits identification of protein elements that are predicted to bind target DNA sequences and thereby regulate gene transcription in H. pylori.