Role of Intra-arterial Nitroglycerin (Post Procedural, Prehemostasis) to Reduce Radial Artery Occlusion after Transradial Catheterisation: A Doppler-guided Study.

The study was intended to evaluate efficacy of Intra-arterial nitroglycerin through the sheath at the end of a transradial procedure to preserve the patency of the radial artery. This prospective observational study was done in the Department of Cardiology, National Institute of Cardiovascular Diseases (NICVD), Dhaka, Bangladesh from May 2017 to April 2018, by including a total 200 patients undergoing coronary procedures (CAG and / or PCI) through TRA. RAO was defined as an absence of antegrade flow or monophasic flow or invert flow on Doppler study. In this study 102 patients (Group I) received 200 mcg intra-arterial nitroglycerine, prior to trans-radial sheath removal. Another 98 patients (Group II) did not receive intra-arterial nitroglycerine prior to trans-radial sheath removal. Conventional haemostatic compression methods were applied (average 2 hours) in both groups of patients. Evaluation of radial arterial arterial blood flow by colour Doppler study was done on next day after the procedure in both groups. Results of this study in which RAO was determined by vascular doppler study showed that frequency of radial artery occlusion were 13.5% one day after transradial coronary procedures. We found the incidence was 8.8% vs. 18.4%, (p=0.04) in Group I and Group II respectively. The incidence of RAO was significantly lower in post procedural nitroglycerine group. From multivariate logistic regression analysis diabetes mellitus (p = 0.02), hemostatic compression time for more than 02 hours after sheath removal (p = <0.001) and procedure time (p = 0.02) was predictors of RAO. So, the administration of nitroglycerin at the end of a transradial catheterization reduced the incidence of RAO, as shown by 1 day after the radial procedure by doppler ultrasound.

Conservative Management Of Partial-Thickness Scald Burns In Children Using Cultured Allogenic Keratinocyte Spray: Initial Experience Of 18 Patients Treated In An Outpatient Setting.

The objective of this study was to describe our clinical experience with the use of cultured allogeneic keratinocyte (CAK) using a simplified cell delivery method in the treatment of pediatric partial-thickness scald burns treated as outpatients in a Burn Unit. An actuator fitted onto a 3ml syringe was used for cell spray. Eighteen patients having active mixed partial-thickness burn wound areas of <10% total body surface area (TBSA), treated between 2017 and 2019, were included in the study. The wounds were managed conservatively with a combination of burn dressings using hydrogels and CAK application. The timing of the CAK application was decided by the treating plastic surgeon based on his clinical judgment and the clinical status of the wound. The primary study endpoints were the number of days and dressing changes required for complete wound reepithelialization. All of the eighteen patients' wounds reepithelialized completely with CAK application, with a mean reepithelialization time of 10.33 (±4.95) days after the application of CAK. The median value for the number of CAK applications and total dressing sessions required to achieve complete healing were 3 and 4 times, respectively. Wounds treated with CAK application between 8-21 days after burn injury required fewer cell application sessions and fewer dressing changes than wounds treated within seven days and after 21 days from the burn injury. None of the patients reported any adverse reaction related to CAK use. The present study suggests that non-extensive mixed partial-thickness scald burn in children can be successfully treated conservatively using CAK as an adjunct in addition to standard dressing in the outpatient setting.

Le but de cette étude est de décrire notre expérience clinique avec l'utilisation de kératinocytes allogéniques de culture (KAC), en utilisant une méthode simplifiée d'application cellulaire pour le traitement des brûlures intermédiaires de l'enfant par eau chaude, traitées en ambulatoire dans notre unité de brûlés. Un embout, fixé à une seringue de 3 ml, a été utilisé pour la vaporisation cellulaire. 18 patients présentant des brûlures de profondeur intermédiaire au stade aigu, de surface <10% de la surface corporelle totale (SCT) et pris en charge entre 2017 et 2019, ont été inclus dans cette étude. Les plaies ont reçu un traitement conservateur combinant des pansements à base d'hydrogel et l'application de KAC. Le moment pour appliquer les KAC a été choisi par le chirurgien plasticien référent en fonction de son appréciation clinique et du stade de la plaie. Les critères principaux d'évaluation de l'étude ont été le nombre de jours et le nombre de réfections de pansements nécessaires à une réépithélialisation complète. Les plaies des 18 patients ont été totalement réépithélialisées par l'application de KAC, avec un délai moyen de 10,33 (+/-4,95) jours après la vaporisation cellulaire. La valeur médiane du nombre d'applications de KAC d'une part et de réfections de pansements d'autre part, nécessaires pour obtenir une cicatrisation complète a été respectivement de trois applications de KAC et de quatre pansements. Les plaies traitées par l'application de KAC dans un délai de 8 à 21 jours après la brûlure ont nécessité moins de séances d'application cellulaire et de pansements que les plaies traitées dans les sept premiers jours ou au-delà du 21e jour après la brûlure. Aucun des patients n'a présenté d'effets secondaires rapportés à l'utilisation de KAC. Cette étude suggère que les brûlures peu étendues intermédiaires par ébouillantement chez l'enfant peuvent être menées à cicatrisation par un traitement conservateur utilisant la vaporisation de KAC en complément de pansements standards en traitement ambulatoire.

A Pilot Study To Compare Nutrition Screening Tools: Customized Nutrition Screening Tool for Burn Patients (Nstb) and Malnutrition Universal Screening Tool (Must).

Nutrition screening is an initial procedure in which the risk of malnutrition is identified. It plays a role in and can incur costs to health systems and patients. A customized nutrition screening tool for burn patients (NSTB) was formulated and the nutritional risk score of 22 patients from a burn unit in Bahrain using NSTB and MUST was compared. The samples selected were adult patients aged 18 years or over; pregnant and mentally retarded patients were excluded. Mean age of the total sample was 29.40, and 90.9% were male. Mean BMI was 26.96. The mean and SD for NSTB was 2.18±1.65, and for MUST 2.0±0.0. A difference in the nutritional screening risk score of the same group of patients was observed. In the MUST group, 100% patients were classified as high risk, while in the NSTB group 50% patients were classified as high risk, 36.36% as moderate risk and 13.63% as low risk respectively. The variability of the risk score in the NSTB group helps prioritize the patients based on high, medium, and low risk, whereas MUST categorizes all patients as high risk. A unique screening tool for burns will be more effective in determining risk patients due to tailor-made characteristics. Even though the data sample is small, the difference gives scope for extensive study.

L'évaluation du risque de dénutrition est nécessaire chez les patients brûlés, chez qui elle joue un rôle majeur dans l'évolution initiale. NSTB a été développé afin de ne pas passer à côté, et a été comparé à MUST au moyen d'une étude piloté réalisé auprès de 22 patients adultes (femmes enceintes et handicapés mentaux exclus) hospitalisés dans un CTB de Bahreïn. L'âge moyen était de 24,9 ans ; 90,9% étaient des hommes, le BMI moyen était de 29,96. Tous les patients de MUST était classés à haut risque quand était variable en utilisant NSTB. En effet, il classait 50% des patients à haut risque; 36,36% à risque modéré et 13,63% à risque faible. Ainsi, NSTB pourrait être plus précis que MUST pour évaluer le risque nutritionnel chez les brûlés, ce qui devrait être validé sur une série plus longue.

Melanocyte-Keratinocyte Transplantation in Post-Burn Leukoderma Scars: Preliminary Experience Using a Modified Technique.

Post-burn leukoderma, commonly affecting the African and Asian communities, results from deep dermal burns. The associated stigma exacerbates the condition and significantly affects the rehabilitation and reintegration of post-burn survivors into society. Melanocyte-keratinocyte transplantation (MKTP) is a promising single-stage treatment for repigmentation in vitiligo. However, its use in post-burn leukoderma is undetermined. This study aims to evaluate the MKTP treatment in post-burn leukoderma patches. Six patients (five males and one female, mean age = 29±5.51 years) with ten patches of post-burn leukoderma underwent single-stage MKTP without adjuvant pigmentation therapy. The postoperative follow-up period ranged from twelve to twenty-four months for all the patients. The average size of leukoderma treated was 16.25±9 cm2. Repigmentation was observed in 92.16±11.05% of the total treated area by the end of one year after MKTP application. All six patients were satisfied with the treatment outcome. MKTP without adjuvant therapy is an effective surgical treatment to treat post-burn leukoderma patches. Future studies should cover a larger sample over a longer follow-up period.

Le vitiligo cicatriciel après brûlure est fréquent dans les populations africaines et asiatiques, affectant significativement la réintégration sociale des patients. La TMK est une technique en 1 temps de repigmentation du vitiligo, prometteuse, qui n'a pas été évaluée dans ce contexte. Nous l'avons utilisée, sans traitement adjuvant, chez 6 patients (5 hommes et 1 femme de 29 +/- 5,51 ans) sur 10 zones dépigmentées (surface de 16,25 +/- 9 cm2), avec un recul de 12 à 32 mois. À un an, une repigmentation a été observée sur 92,16 +/- 11,05% de la surface traitée et tous les patients étaient satisfaits du résultat. La TMK isolée semble donc être efficace pour traiter le vitiligo cicatriciel après brûlures, des études sur des zones plus étendues et avec un suivi à plus long terme restant nécessaires.

Effects of fluid restriction on measures of circulatory efficacy in adults with septic shock.

BACKGROUND: The haemodynamic consequences of fluid resuscitation in septic shock have not been fully elucidated. Therefore, we assessed circulatory effects in the first 24 h of restriction of resuscitation fluid as compared to standard care in intensive care unit (ICU) patients with septic shock. METHODS: This was a post-hoc analysis of the multicentre CLASSIC randomised trial in which patients with septic shock, who had received the initial fluid resuscitation, were randomised to a protocol restricting resuscitation fluid or a standard care protocol in nine ICUs. The highest plasma lactate, highest dose of noradrenaline, and the urinary output were recorded in five time frames in the first 24 h after randomisation. We used multiple linear mixed effects models to compare the two groups. RESULTS: We included all 151 randomised patients; the cumulated fluid resuscitation volume in the first 24 h after randomisation was median 500 ml (Interquartile range (IQR) 0-1500) and 1250 ml (500-2500) in the fluid restriction group and standard care group, respectively. The estimated differences in the fluid restriction group vs. the standard care group were 0.1 mM (95% confidence interval -0.7 to 0.9; P = 0.86) for lactate, 0.01 µg/kg/min (-0.02 to 0.05; P = 0.48) for dose of noradrenaline, and -0.1 ml/kg/h (-0.3 to 0.2; P = 0.70) for urinary output during the first 24 h after randomisation. CONCLUSIONS: We observed no indications of worsening of measures of circulatory efficacy in the first 24 h of restriction of resuscitation fluid as compared with standard care in adults with septic shock who had received initial resuscitation.

Typical patterns of expiratory flow and carbon dioxide in mechanically ventilated patients with spontaneous breathing.

Incomplete expiration of tidal volume can lead to dynamic hyperinflation and auto-PEEP. Methods are available for assessing these, but are not appropriate for patients with respiratory muscle activity, as occurs in pressure support. Information may exist in expiratory flow and carbon dioxide measurements, which, when taken together, may help characterize dynamic hyperinflation. This paper postulates such patterns and investigates whether these can be seen systematically in data. Two variables are proposed summarizing the number of incomplete expirations quantified as a lack of return to zero flow in expiration (IncExp), and the end tidal CO2 variability (varETCO2), over 20 breaths. Using these variables, three patterns of ventilation are postulated: (a) few incomplete expirations (IncExp < 2) and small varETCO2; (b) a variable number of incomplete expirations (2 ≤ IncExp ≤ 18) and large varETCO2; and (c) a large number of incomplete expirations (IncExp > 18) and small varETCO2. IncExp and varETCO2 were calculated from data describing respiratory flow and CO2 signals in 11 patients mechanically ventilated at 5 levels of pressure support. Data analysis showed that the three patterns presented systematically in the data, with periods of IncExp < 2 or IncExp > 18 having significantly lower variability in end-tidal CO2 than periods with 2 ≤ IncExp ≤ 18 (p < 0.05). It was also shown that sudden change in IncExp from either IncExp < 2 or IncExp > 18 to 2 ≤ IncExp ≤ 18 results in significant, rapid, change in the variability of end-tidal CO2 p < 0.05. This study illustrates that systematic patterns of expiratory flow and end-tidal CO2 are present in patients in supported mechanical ventilation, and that changes between these patterns can be identified. Further studies are required to see if these patterns characterize dynamic hyperinflation. If so, then their combination may provide a useful addition to understanding the patient at the bedside.

A mathematical model approach quantifying patients' response to changes in mechanical ventilation: Evaluation in pressure support.

PURPOSE: This article evaluates how mathematical models of gas exchange, blood acid-base status, chemical respiratory drive, and muscle function can describe the respiratory response of spontaneously breathing patients to different levels of pressure support. METHODS: The models were evaluated with data from 12 patients ventilated in pressure support ventilation. Models were tuned with clinical data (arterial blood gas measurement, ventilation, and respiratory gas fractions of O2 and CO2) to describe each patient at the clinical level of pressure support. Patients were ventilated up to 5 different pressure support levels, for 15 minutes at each level to achieve steady-state conditions. Model-simulated values of respiratory frequency (fR), arterial pH (pHa), and end-tidal CO2 (FeCO2) were compared to measured values at each pressure support level. RESULTS: Model simulations compared well to measured data with Bland-Altman bias and limits of agreement of fR of 0.7 ± 2.2 per minute, pHa of -0.0007 ± 0.019, and FeCO2 of -0.001 ± 0.003. CONCLUSION: The models describe patients' fR, pHa, and FeCO2 response to changes in pressure support with low bias and narrow limits of agreement.

A mathematical model approach quantifying patients' response to changes in mechanical ventilation: evaluation in volume support.

This paper presents a mathematical model-approach to describe and quantify patient-response to changes in ventilator support. The approach accounts for changes in metabolism (V̇O2, V̇CO2) and serial dead space (VD), and integrates six physiological models of: pulmonary gas-exchange; acid-base chemistry of blood, and cerebrospinal fluid; chemoreflex respiratory-drive; ventilation; and degree of patients' respiratory muscle-response. The approach was evaluated with data from 12 patients on volume support ventilation mode. The models were tuned to baseline measurements of respiratory gases, ventilation, arterial acid-base status, and metabolism. Clinical measurements and model simulated values were compared at five ventilator support levels. The models were shown to adequately describe data in all patients (χ(2), p > 0.2) accounting for changes in V̇CO2, VD and inadequate respiratory muscle-response. F-ratio tests showed that this approach provides a significantly better (p < 0.001) description of measured data than: (a) a similar model omitting the degree of respiratory muscle-response; and (b) a model of constant alveolar ventilation. The approach may help predict patients' response to changes in ventilator support at the bedside.

Bone-marrow-derived mesenchymal stem cells attenuate cognitive deficits in an endothelin-1 rat model of stroke.

PURPOSE: Stroke is the third leading cause of death and permanent disability in the United States, often producing long-term cognitive impairments, which are not easily recapitulated in animal models. The goals of this study were to assess whether: (1) the endothelin-1 (ET-1) model of chronic stroke produced discernable cognitive deficits; (2) a spatial operant reversal task (SORT) would accurately measure memory deficits in this model; and (3) bone-marrow-derived mesenchymal stem cells (BMMSCs) could reduce any observed deficits. METHODS: Rats were given unilateral intracerebral injections of vehicle or ET-1, a stroke-inducing agent, near the middle cerebral artery. Seven days later, they were given intrastriatal injections of BMMSCs or vehicle, near the ischemic penumbra. The cognitive abilities of the rats were assessed on a novel SORT, which was designed to efficiently distinguish cognitive deficits from potential motoric confounds. RESULTS: Rats given ET-1 had significantly more cognitive errors at six weeks post-stroke on the SORT, and that these deficits were attenuated by BMMSC transplants. CONCLUSIONS: These findings indicate that: (1) the ET-1 model produces chronic cognitive deficits; (2) the SORT efficiently measures cognitive deficits that are not confounded by motoric impairment; and (3) BMMSCs may be a viable treatment for stroke-induced cognitive dysfunction.

Link between automated coronary calcium volumes from intravascular ultrasound to automated carotid IMT from B-mode ultrasound in coronary artery disease population.

AIM: Establishing relationship between coronary calcium volumes from Intravascular Ultrasound (IVUS) and automated carotid intima-media thickness (cIMT) helps in understanding the genetic nature of atherosclerosis disease. In this research, we have quantified the detected calcium from IVUS video frames and associated a relationship between coronary calcium volumes computed and automated cIMT from B-mode ultrasound. METHODS: Coronary calcium volume is computed from IVUS and auto cIMTs are computed using B-mode ultrasound. An automated computer based application is developed and tested on 100 patient volumes (an average of 2549 frames per volume) to calculate lesion area and normalized coronary calcium volume. We use an integrated approach for volume computation which is based on lesion area per frame. We have measured the normalized volume from the calcium detected video frames using proposed integration method. The cIMT of 100 carotids were measured with novel and dedicated automated software analysis (AtheroEdge™ from AtheroPoint™ LLC, Roseville, CA, USA). RESULTS: The computer-based coronary calcium volume (from IVUS) showed a correlation coefficient with respect to cIMT for left and right carotids as 9.1% and 13.9%, respectively. CONCLUSION: Coronary calcium volume computed from IVUS and auto cIMT are moderately correlated. The association between auto cIMT (right side) vs. computer-based coronary calcium volume (IVUS) is stronger than the association between auto cIMT (left side) vs. computer-based coronary calcium volume.

Automated and accurate carotid bulb detection, its verification and validation in low quality frozen frames and motion video.

AIM: Carotid intima-media thickness (cIMT) measurements during clinical trials need to have a fixed reference point (also called as bulb edge points) in the anatomy from which the cIMT can be measured. Identification of the bulb edge points in carotid ultrasound images faces the challenge to be detected automatically due to low image quality and variations in ultrasound images, motion artefacts, image acquisition protocols, position of the patient, and orientation of the linear probe with respect to bulb and ultrasound gain controls during acquisition. METHODS: This paper presents a patented comprehensive methodology for carotid bulb localization and bulb edge detection as a reference point. The method consists of estimating the lumen-intima borders accurately using classification paradigm. Transition points are located automatically based on curvature characteristics. Further we verify and validate the locations of bulb edge points using combination of several local image processing methods such as (i) lumen-intima shapes, (ii) bulb slopes, (iii) bulb curvature, (iv) mean lumen thickness and its variations, and (v) geometric shape fitting. RESULTS: Our database consists of 155 ultrasound bulb images taken from various ultrasound machines with varying resolutions and imaging conditions. Further we run our automated system blindly to spot out the bulbs in a mixture database of 336 images consisting of bulbs and no-bulbs. We are able to detect the bulbs in the bulb database with 100% accuracy having 92% as close as to a neurologists's bulb location. Our mean lumen-intima error is 0.0133 mm with precision against the manual tracings to be 98.92%. Our bulb detection system is fast and takes on an average 9 seconds per image for detection for the bulb edge points and 4 seconds for verification/validation of the bulb edge points.

Clinical significance of aberrant vimentin expression in oral premalignant lesions and carcinomas.

OBJECTIVE: To investigate the clinical significance of vimentin expression at early and late events of tobacco/areca nut-associated oral tumorigenesis. MATERIALS AND METHODS: Immunohistochemistry (IHC) was carried out on paraffin-embedded tissues of oral mucosa normal (n = 10), inflammatory lesions (n = 19), leukoplakia (n = 52), submucous fibrosis (n = 71) and tumours/cut margins (n = 227 each), using anti-vimentin antibody, and the expression profile was correlated with patients' clinical parameters. Immunofluorescence, Western blot and RT-PCR analysis were also carried out wherever adequate and fresh tissues were available. RESULTS: Aberrant vimentin expression was seen in hyperplastic, dysplastic and fibrotic tissues, which showed statistically significant correlation with the histopathological grade of dysplasia (P = 0.001) and fibrosis (P = 0.009). Vimentin expression also showed statistically significant correlation with tumour size (P = 0.048), clinical stage (P = 0.013), regional lymph node metastases (P = 0.001), local recurrence (P = 0.001) and survival (P = 0.021) of patients with oral squamous cell carcinoma (OSCC). Its expression in invasive fronts statistically correlated with development of nodal metastasis and local recurrence. CONCLUSIONS: Our results suggest possible role of vimentin in early events of tobacco/areca nut-associated oral tumorigenesis, which may prove useful to predict the malignant potential of high-risk oral lesions. Further, association between vimentin expression in invasive fronts and aggressive phenotype of tumours may help clinicians to choose the appropriate treatment modality for OSCC management.

Antioxidative responses of Salvinia (Salvinia natans Linn.) to aluminium stress and it's modulation by polyamine.

Antioxidative stress response of free-floating aquatic fern (Salvinia natans Linn.) was studied under increasing toxic amount of aluminium (Al) and its modulation by exogenous application of polymaine. Increased levels of superoxide (O2 (-)) and hydrogen peroxide (H2O2) species from affected tissues suggested that plants were undergoing oxidative stress and it was concominant with increased accumulation of Al in a dose dependent manner. Application of polyamine like putrescine (Put) led to a decrease in oxidative stress as revealed by reduced level of O2 (-) and H2O2. Al toxicity resulted into decreased biomass that was ameliorated by the application of Put. The changes observed in lipid peroxidation (MDA) and protein oxidation also indicated that plats are undergoing Al induced oxidative stress. In order to circumvent the oxidative stress resulting from Al toxicity, plants enzymatic and nonenzymatic antioxidant pathways were active. The ratio of both oxidized and reduced cellular glutathione exhibited significant variation in response to Al stress and was improved upon Put treatment. Peroxidase and glutathione were upregulated whereas catalse was downregulated under varying doses of Al. Isozyme profile of above enzymes also showed a trend with increasing amount of Al. The nuclear disintegration study using comet assay was indicative of Al induced oxidative stress. In the present study, we have explored the antioxidative response of aquatic fern Salvinia natans Linn in response to Al toxicity. The application of polyamine Put improved the overall antioxidative response and thus would make it a better candidate to be used as hyper accumulator of Al and other toxic metals.

Assessing the potential clinical utility of transplantations of neural and mesenchymal stem cells for treating neurodegenerative diseases.

Treatments for neurodegenerative diseases have little impact on the long-term patient health. However, cellular transplants of neuroblasts derived from the aborted embryonic brain tissue in animal models of neurodegenerative disorders and in patients have demonstrated survival and functionality in the brain. However, ethical and functional problems due to the use of this fetal tissue stopped most of the clinical trials. Therefore, new cell sources were needed, and scientists focused on neural (NSCs) and mesenchymal stem cells (MSCs). When transplanted in the brain of animals with Parkinson's or Huntington's disease, NSCs and MSCs were able to induce partial functional recovery by promoting neuroprotection and immunomodulation. MSCs are more readily accessible than NSCs due to sources such as the bone marrow. However, MSCs are not capable of differentiating into neurons in vivo where NSCs are. Thus, transplantation of NSCs and MSCs is interesting for brain regenerative medicine. In this chapter, we detail the methods for NSCs and MSCs isolation as well as the transplantation procedures used to treat rodent models of neurodegenerative damage.

Variations of antioxidative responses in two rice cultivars with polyamine treatment under salinity stress.

The rice varieties viz. Nonabokra and Swarna were evaluated on the basis of their responses for oxidative stress induced by sodium chloride (NaCl) and the effects of exogenously applied polyamine thereon. Rice seedlings were treated with 200 mM of NaCl supplemented with two dosages: 1 mM and 2 mM putrescine. Following treatments, plants were evaluated for accumulation of reactive oxygen species (ROS) like O2 (-), H2O2 etc. in tissues, lipid peroxidation, protein carbonylation, accumulation of flavonoids and anthocyanin, activities of different oxidative enzymes like guaiacol peroxidase (GPX), catalase (CAT) and glutathione reductase (GR). Preliminary, oxidative stress out of salinity was ensured by plants from significantly higher accumulation of O2 (-) and H2O2 in the tissues of the NaCl treated varieties. Irrespective of varieties, there recorded a significant variation of the endogenous polyamine profiles under NaCl stress. Interestingly, exogenous application of putrescine had a close relationship on O2 (-) and H2O2 content for both the varieties. However, Nonabokra was evident as more respondent than Swarna to applied putrescine. The other effects of oxidative stress was impacted on plants as higher values of MDA content, enhanced rate of protein oxidation and putrescine recorded as an alleviating agent regardless of varieties with dose dependant manner. The generation of ROS and cellular disintegration was accompanied by up regulation of non-enzymatic and enzymatic antioxidation pathways with exogenous application of putrescine. For non-enzymatic antioxidant, it revealed that putrescine was highly effective for sustaining the anthocyanin and flavonoid content in both the varieties under salinity. Whereas, antioxidative enzyme, CAT showed its diminished activity; but activity of GPX and GR were significantly induced under salinity and it was according to the concentration of applied putrescine.

Stimulatory lipids accumulate in the mouse liver within 30 min of contact sensitization to facilitate the activation of Naïve iNKT cells in a CD1d-dependent fashion.

Natural killer T cells with invariant αß-T cell receptors (TCRs) (iNKT cells) constitute a lipid-responsive arm of the innate immune system that has been implicated in the regulation or promotion of various immune, infectious and neoplastic processes. Contact sensitivity (CS), also known as contact hypersensitivity or allergic contact dermatitis, is one such immune process that begins with topical sensitization to an allergen and culminates in a localized cutaneous inflammatory response after challenge with the same allergen. CS depends on events initiated early in sensitization by hepatic iNKT cells. We have shown previously that these iNKT cells release IL-4 early after skin sensitization to activate B-1 B cells to produce IgM antibodies that aid in local recruitment of the effector T cells. Here, we utilize adoptive transfer techniques in several strains of knockout mice to demonstrate that hepatic lipids isolated 30 min after sensitization are significantly more stimulatory to naïve hepatic iNKT cells than hepatic lipids isolated after sham sensitization. These stimulatory hepatic lipids specifically affect iNKT cells and not B-1 B cells. The downstream CS response is abrogated with anti-CD1d-blocking antibodies, suggesting a critical role of CD1d in the activation of hepatic iNKT cells with these lipids. Hepatocytes may not be essential, as donor hepatic iNKT cells can reconstitute CS without migrating to the recipient mouse liver. Rather, CD1d-expressing liver mononuclear cells are sufficient for activation of iNKT cells. In conclusion, stimulatory lipids accumulate in the liver soon after sensitization and facilitate iNKT cell activation in a CD1d-dependent yet potentially hepatocyte-independent manner.

Invited review: cGMP-dependent protein kinase signaling mechanisms in smooth muscle: from the regulation of tone to gene expression.

cGMP is a second messenger that produces its effects by interacting with intracellular receptor proteins. In smooth muscle cells, one of the major receptors for cGMP is the serine/threonine protein kinase, cGMP-dependent protein kinase (PKG). PKG has been shown to catalyze the phosphorylation of a number of physiologically relevant proteins whose function it is to regulate the contractile activity of the smooth muscle cell. These include proteins that regulate free intracellular calcium levels, the cytoskeleton, and the phosphorylation state of the regulatory light chain of smooth muscle myosin. Other studies have shown that vascular smooth muscle cells (VSMCs) that are cultured in vitro may cease to express PKG and will, coincidentally, acquire a noncontractile, synthetic phenotype. The restoration of PKG expression to the synthetic phenotype VSMC results in the cells acquiring a more contractile phenotype. These more recent studies suggest that PKG controls VSMC gene expression that, in turn, regulates phenotypic modulation of the cells. Therefore, the regulation of PKG gene expression appears to be linked to phenotypic modulation of VSMC. Because several vascular disorders are related to the accumulation of synthetic, fibroproliferative VSMC in the vessel wall, it is likely that changes in the activity of the nitric oxide/cGMP/PKG pathway is involved the development of these diseases.