A case of relapsing chronic eosinophilic pneumonia treated by Omalizumab.

Chronic eosinophilic pneumonia (CEP) is an idiopathic disorder characterized by an abnormal accumulation of eosinophils in the pulmonary interstitial and alveolar spaces. Although many patients respond very well to treatment by steroids, some suffer from disease relapse. There aren't many treatment alternatives for steroid dependent patients or patients who are steroid intolerant because of their side effects. In the following article, we report the case of a 68 years old lady suffering from a relapsing CEP and severe osteoporosis successfully treated with Omalizumab.

Case series of endoscopic treatment of post-intubation tracheal stenosis.

INTRODUCTION: Benign tracheal stenosis is a common problem encountered after tracheal intubation or tracheostomy. It can be managed by surgical or nonsurgical techniques. This case series describes the outcome of 11 cases of endobronchial treatment for complex tracheal stenoses. METHODS: A retrospective study was carried out in two hospitals in Lebanon. Patients were contacted on a regular basis for 6 months and asked about the presence of dyspnea and its characteristics. RESULTS: The most common presenting symptom was inspiratory stridor. Five patients (45.45%) were not satisfied after the bronchoscopic intervention. Six patients (54.55%) were satisfied with the outcome. All were initially treated with argon plasma coagulation and dilation. If any persistent symptoms were present, stenting was done. Three patients had a stent placement. Failure of stenting occurred with two patients. None of the satisfied patients had any early symptoms. CONCLUSION: Bronchoscopic interventions yielded acceptable results when treating complex stenoses. More data is still needed to guide physicians for better approaches. When confronting complex tracheal stenosis, a multidisciplinary approach between surgical and nonsurgical doctors is preferred to choose the best medical care.

A Liposarcoma Arising in a Pulmonary Hamartoma, Coexisting With Benign Metastasizing Leiomyoma.

Pulmonary hamartoma is a common benign tumor that rarely degenerates into malignancy. This report documents a unique case of pulmonary hamartoma with malignant transformation into well-differentiated liposarcoma, coexisting in proximity to pulmonary nodules representing benign metastasizing leiomyoma in a 60-year-old woman.

Pneumoscrotum Caused by a Bronchopleural Fistula.

Pneumoscrotum is the term used to indicate the presence of air in the scrotum and comprises scrotal emphysema and pneumatocele. It is an uncommon medical condition and encompasses multiple etiologies, some of which may be life-threatening. We present the case of a 45-year-old male who developed a pneumoscrotum seven days after undergoing a thoracoscopy with decortication, pleural biopsy, and chest tube insertion, for a loculated pleural effusion not amenable to drainage by a pigtail catheter. The patient was diagnosed with a bronchopleural fistula and was treated conservatively with negative chest tube pressure. Treatment of the fistula and of the resulting pneumothorax allowed resorption of the pneumoscrotum. The associated literature is reviewed after the case presentation. This case report underlines the importance of evaluating a pneumoscrotum that should not be underestimated.

Ligand-specific recycling profiles determine distinct potential for chronic analgesic tolerance of delta-opioid receptor (DOPr) agonists.

δ-opioid receptor (DOPr) agonists have analgesic efficacy in chronic pain models but development of tolerance limits their use for long-term pain management. Although agonist potential for inducing acute analgesic tolerance has been associated with distinct patterns of DOPr internalization, the association between trafficking and chronic tolerance remains ill-defined. In a rat model of streptozotocin (STZ)-induced diabetic neuropathy, deltorphin II and TIPP produced sustained analgesia  following daily (intrathecal) i.t. injections over six days, whereas similar treatment with SNC-80 or SB235863 led to progressive tolerance and loss of the analgesic response. Trafficking assays in murine neuron cultures showed no association between the magnitude of ligand-induced sequestration and development of chronic tolerance. Instead, ligands that supported DOPr recycling were also the ones producing sustained analgesia over 6-day treatment. Moreover, endosomal endothelin-converting enzyme 2 (ECE2) blocker 663444 prevented DOPr recycling by deltorphin II and TIPP and precipitated tolerance by these ligands. In conclusion, agonists, which support DOPr recycling, avoid development of analgesic tolerance over repeated administration.

Acute Respiratory Distress Syndrome Secondary to Radiotherapy for Breast Cancer: A Case Report.

BACKGROUND Radiotherapy is often used as an adjuvant therapy in breast cancer following surgical resection of the primary malignant tumor. It has multiple respiratory side effects, but acute respiratory distress syndrome (ARDS) is a rare complication. We describe here the case of a woman with breast cancer who developed ARDS 1 week after her final radiotherapy session. CASE REPORT A 69-year-old female with breast cancer presented 1 week after her final session of radiotherapy. She had developed a sudden onset of hypotension unresponsive to fluids, oxygen desaturation unresponsive to high flow oxygen, and new bilateral infiltrates had appeared on chest x-ray (CXR) predominant in the left upper lobe, which was interestingly the main area affected by the radiotherapy beams. A diagnosis of atypical ARDS secondary to radiotherapy was established. She was intubated and a low tidal volume/high positive end-expiratory pressure (PEEP) strategy was utilized to manage her condition. After 48 hours, the infiltrates diminished remarkably, and she was extubated the following day. On discharge, she had a completely normal CXR; a computed tomography (CT) chest performed 1 month later showed complete resolution of the alveolar opacities. CONCLUSIONS ARDS remains an extremely rare complication of thoracic radiotherapy. However, physicians must be wary of its development in order to diagnose it quickly and treat accordingly.

Localization and Interaction between Kinin B1 Receptor and NADPH Oxidase in the Vascular System of Diabetic Rats.

Kinin B1 receptor (B1R) enhanced superoxide anion ([Formula: see text]) production in the vasculature of diabetic rats. This study investigates the induction and distribution of B1R in diabetic blood vessels and addresses the hypothesis that B1R is co-localized with NADPH oxidase (NOX1 and NOX2) and produces its activation via protein kinase C (PKC). Diabetes was induced in rats with streptozotocin (STZ 65 mg.kg-1, i.p.). Two weeks later, the production of [Formula: see text] was measured in aorta rings in response to the B1R agonist (Sar[D-Phe8]-des-Arg9-BK, 20 µM) by the method of lucigenin-enhanced chemiluminescence. Various inhibitors were added (10 µM) to block PKCtotal (Ro-31-8220), PKCß1/2 (LY333531), or NADPH oxidase (Diphenyleneiodonium). The cellular localization of B1R was studied in the aorta, popliteal artery, and renal glomerulus/arteries by immunofluorescence and confocal microscopy with markers of endothelial cells (anti-RECA-1), macrophages (anti-CD11), vascular smooth muscle cells (anti-SMA), and NADPH oxidase (anti-NOX1 and NOX2). Although B1R was largely distributed in resistant vessels, it was sparsely expressed in the aorta's endothelium. The greater basal production of [Formula: see text] in STZ-diabetic aorta was significantly enhanced by the B1R agonist (15-45 min). The peak response to the agonist (30 min) was inhibited by all inhibitors. Immunofluorescent staining for B1R, NOX1, and NOX2 was significantly increased in endothelial cells, vascular smooth muscle cells, and macrophages of STZ-diabetic aorta on which they were found co-localized. Data showed that B1R enhanced [Formula: see text] by activating vascular NADPH oxidase through PKCß1/2. This was substantiated by the cellular co-localization of B1R with NOX1 and NOX2 and opens the possibility that B1R-enhanced oxidative stress is derived from vascular and infiltrating immune cells in diabetes.

Argan Oil as an Effective Nutri-Therapeutic Agent in Metabolic Syndrome: A Preclinical Study.

The present study aims at examining the effects of argan oil on the three main cardiovascular risk factors associated with metabolic syndrome (hypertension, insulin resistance and obesity) and on one of its main complications, neuropathic pain. Male Sprague-Dawley rats had free access to a drinking solution containing 10% d-glucose or tap water for 12 weeks. The effect of argan oil was compared to that of corn oil given daily by gavage during 12 weeks in glucose-fed rats. Glucose-fed rats showed increases in systolic blood pressure, epididymal fat, plasma levels of triglycerides, leptin, glucose and insulin, insulin resistance, tactile and cold allodynia in association with a rise in superoxide anion production and NADPH oxidase activity in the thoracic aorta, epididymal fat and gastrocnemius muscle. Glucose-fed rats also showed rises in B1 receptor protein expression in aorta and gastrocnemius muscle. Argan oil prevented or significantly reduced all those anomalies with an induction in plasma adiponectin levels. In contrast, the same treatment with corn oil had a positive impact only on triglycerides, leptin, adiponectin and insulin resistance. These data are the first to suggest that argan oil is an effective nutri-therapeutic agent to prevent the cardiovascular risk factors and complications associated with metabolic syndrome.

Kininase 1 As a Preclinical Therapeutic Target for Kinin B1 Receptor in Insulin Resistance.

Kinin B1 receptor (B1R) contributes to insulin resistance, an early event in type 2 diabetes, through the upregulation and activation of the inducible form of nitric oxide synthase (iNOS), pro-inflammatory cytokines and the oxidative stress. This study addresses the hypothesis that inhibition of kininase 1 (carboxypeptidase M, CPM), the key enzyme involved in the biosynthesis of B1R agonists, could exert the same beneficial effects to B1R antagonism in insulin resistance. Male Sprague-Dawley rats were made insulin resistant with a drinking solution containing 10% D-glucose for a period of 9 weeks. Control rats received tap water. During the last week, kininase 1 was blocked with Mergetpa (1 mg kg-1 twice daily, s.c.) and the impact was determined on insulin resistance (HOMA index), metabolic hormone levels, oxidative stress and the expression of several markers of inflammation by western blot and qRT-PCR. Glucose-fed rats displayed hyperglycemia, hyperinsulinemia, hyperleptinemia, insulin resistance, hypertension, positive body weight gain, and enhanced expression of B1R, CPM, iNOS, and IL-1ß in renal cortex, aorta and liver. Markers of oxidative stress (superoxide anion and nitrotyrosine expression) were also enhanced in aorta and renal cortex. Mergetpa reversed and normalized most of those alterations, but failed to affect leptin levels and hypertension. Pharmacological blockade of kininase 1 (CPM) exerted similar beneficial effects to a 1-week treatment with a B1R antagonist (SSR240612) or an iNOS inhibitor (1,400 W). These data reinforce the detrimental role of B1R in insulin resistance and recommend CPM as a new therapeutic target.

Beneficial effects of argan oil on blood pressure, insulin resistance, and oxidative stress in rat.

OBJECTIVE: The aim of the present study was to investigate whether a 5-wk treatment with argan oil, which is known for its antioxidant properties, can reduce arterial hypertension, hyperglycemia, insulin resistance, and enhanced basal superoxide anion production and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity in the aorta of glucose-fed rats. METHODS: Sprague-Dawley rats had free access to a drinking solution containing 10% d-glucose or tap water (control) for 5 wk. The effect of argan oil in glucose-fed rats was compared with that of corn oil given daily by gavage (5 mL/kg) over a 5-wk period. Oxidative stress was evaluated by measuring the superoxide anion production and the NADPH oxidase activity using the lucigenin method. RESULTS: The 5-wk treatment with glucose led to increases in systolic blood pressure, plasma glucose, and insulin levels as well as an increase in the insulin resistance index in association with a rise in superoxide anion production and NADPH oxidase activity (sensitive to diphenyleneiodonium) in the aorta. The simultaneous treatment with argan oil prevented or significantly reduced all of these effects, yet the same treatment with corn oil had a positive effect only on hyperinsulinemia and insulin resistance. CONCLUSIONS: The findings from the present study demonstrated that argan oil treatment reduced elevation of blood pressure, hyperglycemia, and insulin resistance through its antioxidative properties in glucose-fed rats. Hence, argan oil, which is now available in the market as a consumable food, may be of potential therapeutic value in the treatment of arterial hypertension and insulin resistance.

Interplay between the kinin B1 receptor and inducible nitric oxide synthase in insulin resistance.

BACKGROUND AND PURPOSE: Kinins are vasoactive and pro-inflammatory peptides whose biological effects are mediated by two GPCRs, named B1 and B2 receptors. While the B2 receptor plays a protective role in the cardiovascular system via the activation of endothelial NOS, the B1 receptor is associated with vascular inflammation, insulin resistance and diabetic complications. Because the B1 receptor is a potent activator of the inducible form of NOS (iNOS), this study has addressed the role of iNOS in the deleterious effects of B1 receptors in insulin resistance. EXPERIMENTAL APPROACH: Male Sprague-Dawley rats (50-75 g) had free access to a drinking solution containing 10% d-glucose or tap water (control) for 9 weeks. During the last week, a selective iNOS inhibitor (1400W, 1 mg·kg(-1) twice daily) or its vehicle was administered s.c. KEY RESULTS: Prolonged glucose treatment caused insulin resistance and several hallmarks of type 2 diabetes. Whereas the treatment with 1400W had no impact on the elevated systolic blood pressure and leptin levels in glucose-fed rats, it significantly reversed or attenuated hyperglycaemia, hyperinsulinaemia, insulin resistance (HOMA index), body weight gain, peroxynitrite formation (nitrotyrosine expression) and the up-regulation of biomarkers of inflammation (B1 receptor, carboxypeptidase M, iNOS and IL-1ß) in renal cortex and aorta and to some extent in the liver. CONCLUSIONS AND IMPLICATIONS: Pharmacological blockade of iNOS prevents the formation of peroxynitrite, which amplifies the pro-inflammatory effects of B1 receptors through a positive feedback mechanism. Hence, targeting iNOS can prevent the deleterious effects of B1 receptors in insulin resistance and peripheral inflammation.