Pycnogenol((R)) in the Management of Asthma

Asthma is characterized as a chronic inflammatory process. Pycnogenol((R)), a bioflavonoid mixture extracted from Pinus maritima, is known to scavenge free radicals while possessing antioxidant and antiinflammatory properties. The objective of this study was to evaluate the efficiency of this agent in a randomized, double-blinded, placebo-controlled, crossover study in patients with varying asthma severity. Twenty-six patients who fulfilled the American Thoracic Society criteria for asthma were enrolled in the study. Medical history, physical examination, blood sample analyses, and spirometric values were obtained at baseline, 4 weeks, and 8 weeks. The patients were randomly assigned to receive either 1 mg/lb/day (maximum 200 mg/day) Pycnogenol or placebo for the first period of 4 weeks and then crossed over to the alternate regimen for the next 4 weeks. No adverse effects were observed related to the study drug. Within the contingent of 22 patients who completed the study, almost all responded favorably to Pycnogenol in contrast to placebo. Pycnogenol treatment also significantly reduced serum leukotrienes compared with placebo. The results of this pilot study indicate that Pycnogenol may be a valuable nutraceutical in the management of chronic asthma. We recommend that further clinical trials be conducted in larger groups of asthmatics to establish its efficacy.     

Protection against experimental autoimmune encephalomyelitis by a proteasome modulator

The capacity of interferon beta to alter the course of multiple sclerosis has promoted a new therapeutic concept, based upon the modulation of the immune response rather than its suppression. As the proteasome plays a crucial role in the control of the inflammatory process and immune cell survival, targeting the proteasome appears as a novel approach for the prevention and treatment of inflammatory autoimmune diseases. We have previously shown that ritonavir, an HIV-1 protease inhibitor used in AIDS therapy, can modulate the proteasome function by inhibiting the chymotrypsin-like activity and enhancing the trypsin-like activity. We have, therefore, explored its therapeutic potential on experimental autoimmune encephalomyelitis (EAE), an experimental model of multiple sclerosis, in Lewis rats and SJL mice. Daily administration of ritonavir during autoimmune antigen stimulation prevented clinical symptoms of EAE in a dose- and time-dependent manner. This protection was accompanied by an inhibition of the mononuclear cell infiltration into the central nervous system usually observed in EAE. Despite a complete absence of clinical symptoms during first EAE induction, ritonavir-treated animals became resistant to further induction of EAE, suggesting an immune mechanism of protection. These results suggest that proteasome modulation using ritonavir or analogues may be of interest for patients with multiple sclerosis.     

Standardized percentile curves of body mass index of Iranian children compared to the US population reference.

OBJECTIVE: To present standardized percentile curves of body mass index (BMI) for Iranian children, and compare these to the US population reference. SUBJECTS: 1599 boys and 1702 girls aged 2-18 y living in urban Tehran as a part of a random cluster sample survey of 1 in 1000 families throughout Iran. MEASUREMENTS: Heights (cm) and weights (kg) were collected by trained health staff. RESULTS: Standardized BMI reference curves for Iranian boys and girls were constructed. The curves are shown to fit the data well. The development pattern of BMI for boys and girls are compared. CONCLUSIONS: The major differences observed between Iranian and the US BMI charts underline the need for population-specific reference data. For children over six years the 5th and 95th percentiles of our data may be used provisionally as cut-off points for defining thinness and obesity for Iranian children and adolescents.     

Pharmacokinetic study of dexamethasone disodium phosphate using intravitreal, subconjunctival, and intravenous delivery routes in rabbits.

Dexamethasone is a corticosteroid with proven efficacy for treating both anterior- and posterior-segment ocular diseases. Delivery of drugs to the back of the eye has always been a challenge, with dexamethasone being no exception. There are multiple delivery routes to the retina, with each exhibiting different pharmacokinetics, depending on the drug molecule and specific route of administration. In this study, we used intravenous (IV), subconjunctival (SC), and intravitreal (IVT) injections in rabbits to determine the pharmacokinetics of dexamethasone phosphate and its metabolic product, dexamethasone, at low (25 microg/kg) and high (250 microg/kg) doses. Plasma samples were collected from each group of animals at different time points up to 24 h after the injection. Using a liquid chromatographic mass spectrometric method with a limit of detection of 0.5 ng/mL, the plasma concentration for dexamethasone and its prodrug compound were quantified. IV delivery showed the fastest plasma elimination, followed by SC delivery. IVT delivery exhibited a depot effect, with very low plasma levels throughout the 24-h time course. At 24 h postinjection, only the high-dose IVT and low- and high-dose SC dexamethasone injections were still detectable in the plasma.     

A predictive model for survival after in-hospital cardiopulmonary arrest

BACKGROUND: In-hospital cardiopulmonary resuscitation (CPR) has seen a steady increase in the application of technology and techniques since the introduction of closed cardiac massage in 1960. Despite this progress, there has not been a demonstrated improvement in survival rates after in-hospital cardiac arrest over the last 40 years. Identification of prognostic factors associated with survival after a resuscitation attempt can help physician decisions and patients' end-of-life choices in a pre-arrest situation. METHODS: Using an Utstein-based template we analyzed 219 consecutive adult attempted resuscitations in a large urban teaching hospital over a 3-year period. The main outcome measures were survival to discharge, 1 and 3 months. Backwards stepwise logistic regression was used to select baseline variables that predict survival at discharge, 1 and 3 months. RESULTS: Survival rates at discharge, 1 and 3 months were 15.1, 13.3, and 11.5%. Meaningful neurological status (cerebral performance score of 1) at discharge was achieved in 61% of survivors. Independent predictors of survival were: higher body-mass index (BMI), presence of chronic renal insufficiency (CRI), respiratory arrest, ventricular tachycardia/fibrillation (VT/VF) as initial rhythm and arrest early during the hospital stay. A risk model based on these variables demonstrated a significant fit between predicted and observed survival at discharge with goodness of fit test P-value of 0.87. CONCLUSIONS: Survival after in-hospital cardiopulmonary arrest is poor and can be estimated by using clinical variables. If validated in a large prospective trial, this score could help physicians in attempting resuscitation, patients and families in making end-of-life decisions and hospitals in resource allocation.     

N omega-amino-L-arginine, an inhibitor of nitric oxide synthase, raises vascular resistance but increases mortality rates in awake canines challenged with endotoxin

Inhibitors of nitric oxide synthase (NOS) have been reported to increase mean arterial pressure in animal models of sepsis and recently have been given to patients in septic shock. However, controlled studies to determine the effects of these agents on cardiovascular function and survival in awake animal models of sepsis have not been reported. To examine the therapeutic potential of NOS inhibition in septic shock, we challenged canines with endotoxin (2 or 4 mg/kg i.v.) and treated them with either normal saline or N omega-amino-L-arginine (10 or 1 mg/kg/h), the most specific inhibitor available for the isoform of NOS implicated in septic shock. Endotoxemic animals treated with N omega-amino-L-arginine (n = 11) had higher systemic and pulmonary vascular resistance indices (SVRI and PVRI, p less than or equal to 0.033) and decreased heart rates (p = 0.009), cardiac indices (CI, p = 0.01), oxygen delivery indices (p = 0.027), and oxygen consumption indices (p = 0.046) compared with controls (n = 6). Moreover, N omega-amino-L-arginine increased mortality rates after endotoxin challenge (10 of 11 vs. 1 of 6 controls, p = 0.005). Administration of L-arginine did not improve survival or alter the cardiopulmonary effects of N omega-amino-L-arginine, which suggests that inhibition of NOS may not have been competitive. In normal animals, N omega-amino-L-arginine alone (n = 3) increased SVRI (p = 0.0008) and mean arterial pressure (p = 0.016), and decreased CI (p = 0.01) compared with saline-treated controls (n = 3), but, at the high dose, also produced neuromuscular rigidity and seizure-like activity that was not apparent in the endotoxemic model. Thus, the mortality rate from endotoxemia increased either because of NOS inhibition per se or because of properties unique to N omega-amino-L-arginine, or both.     

Skin-to-skin contact (Kangaroo Care) analgesia for preterm infant heel stick

The purpose of the study was to compare a heel stick conducted during Kangaroo Care (skin-to-skin contact) with the mother to a heel stick in a warmer in reducing premature infant physiologic and behavioral pain responses. Twenty-four premature infants in a university-based neonatal intensive care unit were recruited and randomized to 2 sequences: sequence A group received 3 hours of Kangaroo Care (with a heel stick in Kangaroo Care) followed by 3 hours in a warmer (with a heel stick in the warmer). Sequence B group had warmer care and a heel stick (in the warmer) before Kangaroo Care and a heel stick (in Kangaroo Care). Heart rate, respiratory rate, oxygen saturation, crying time, and behavioral state were measured before, during, and after heel stick. Repeated measures ANOVA and Mann Whitney U statistics were performed. Heart rate and length of crying in response to pain were significantly reduced during Kangaroo Care and the Kangaroo Care heel stick as compared to when infants were in the warmer and had a heel stick in the warmer. Three infants did not cry at all during the Kangaroo Care heel stick; infants slept more during Kangaroo Care than in the warmer. Kangaroo Care positioning before and during heel stick is a simple and inexpensive analgesic intervention to ameliorate pain in stable premature infants.     

A randomized,double‐blind,placebo‐controlled,dose‐finding trial with Lolium perenne peptide immunotherapy

Background

A novel subcutaneous allergen immunotherapy formulation (gpASIT+?) containing Lolium perenne peptides (LPP) and having a short up‐dosing phase has been developed to treat grass pollen–induced seasonal allergic rhinoconjunctivitis. We investigated peptide immunotherapy containing the hydrolysate from perennial ryegrass allergens for the optimum dose in terms of clinical efficacy, immunogenicity and safety.

Methods

This prospective, double‐blind, placebo‐controlled, phase IIb, parallel, four‐arm, dose‐finding study randomized 198 grass pollen–allergic adults to receive placebo or cumulative doses of 70, 170 or 370 μg LPP. All patients received weekly subcutaneous injections, with the active treatment groups reaching assigned doses within 2, 3 and 4 weeks, respectively. Efficacy was assessed by comparing conjunctival provocation test (CPT) reactions at baseline, after 4 weeks and after completion. Grass pollen–specific immunoglobulins were analysed before and after treatment.

Results

Conjunctival provocation test (CPT) response thresholds improved from baseline to V7 by at least one concentration step in 51.2% (170 μg; P = .023), 46.3% (370 μg), and 38.6% (70 μg) of patients receiving LPP vs 25.6% of patients receiving placebo (modified per‐protocol set). Also, 39% of patients in the 170‐μg group became nonreactive to CPT vs 18% in the placebo group. Facilitated allergen‐binding assays revealed a highly significant (P < .001) dose‐dependent reduction in IgE allergen binding across all treatment groups (70 μg: 17.1%; 170 μg: 18.8%; 370 μg: 26.4%). Specific IgG₄ levels increased to 1.6‐fold (70 μg), 3.1‐fold (170 μg) and 3.9‐fold (370 μg) (mPP).

Conclusion

Three‐week immunotherapy with 170 μg LPP reduced CPT reactivity significantly and increased protective specific antibodies.