Efficacy of phytol-derived diterpenoid immunoadjuvants over alum in shaping the murine host's immune response to Staphylococcus aureus

The ubiquitous gram-positive bacterium Staphylococcus aureus occupies a unique niche in humans for its ability to survive both as a commensal and a life-threatening pathogen. Its complex relationship with the host and its ability to engender a throng of virulence factors, have hindered the development of a successful vaccine against it. The use of immunoadjuvants to enhance host immunity and prevent the shift from commensalism to pathogenicity is a rational approach for containing infection. The objective of this study was to understand the mechanisms by which alum and two phytol-derived immunoadjuvants, phytanol (PHIS-01) ¹ and phytanyl chloride (PCl) ² shape the interaction between S. aureus and its murine host. We studied the effects of the phytol derivatives, relative to alum, on the induction of inflammatory cytokines and chemokines, recruitment of CD11b⁺ cells, generation of specific anti-S. aureus antibodies and in vitro clearance of S. aureus. Our results showed that both PHIS-01 and PCl were stronger inducers of protective cytokines IL-17 and IL-1β than alum, and far exceeded alum in enhancing anti-S. aureus antibody response. However, both alum and the phytol derivatives (particularly PCl) promoted efficient recruitment of CD11b⁺ cells. Furthermore, PHIS-01, alum and to a lesser extent, PCl were able to up-regulate the expression of key inflammation-related genes that were highly down-regulated by S. aureus alone. In vitro killing assays showed that both PHIS-01 and PCl were far more potent than alum in promoting S. aureus clearance; this indicated their efficiency in shaping an effective anti-S. aureus immune microenvironment. In summary, our study provides evidence for the better effectiveness of phytol-derived immunoadjuvants over alum in enhancing anti-S. aureus immunity.     

Missing Female Fetus: A Micro Level Investigation of Sex Determination in a Periurban Area of Northern India

A micro-level investigation of 983 pregnant women (aged 15–49 years) regarding sex determination and associated factors was carried out in a periurban region of Northern India. Among the women surveyed, 183 chose to use sex determination. The highest percentage of sex determination was among 30–39-year-old women, and general caste and family size were two risk factors associated with sex determination. Correcting imbalances in sex ratios at birth is a complex issue without easy answers, especially in patriarchal societies. Apart from raising awareness among decisionmakers, property rights in favor of women and strict vigilance and record of registration of ultrasound machines are necessary.     

A lowered salt intake does not compromise iodine status in Cape Town,South Africa,where salt iodization is mandatory

ObjectiveUniversal salt iodization is an effective strategy to optimize population-level iodine. At the same time as salt-lowering initiatives are encouraged globally, there is concern about compromised iodine intakes. This study investigated whether salt intakes at recommended levels resulted in a suboptimal iodine status in a country where salt is the vehicle for iodine fortification.MethodsThree 24-h urine samples were collected for the assessment of urinary sodium and one sample was taken for urinary iodine concentrations (UICs) in a convenience sample of 262 adult men and women in Cape Town, South Africa. Median UIC was compared across categories of sodium excretion equivalent to salt intakes lower than 5, 5 to 9, and greater than or equal to 9 g/d.ResultsThe median UIC was 120 μg/L (interquartile range 75.3–196.3), indicating iodine sufficiency. Less one-fourth (23.2%) of subjects had urinary sodium excretion values within the desirable range (salt <5 g/d), 50.7% had high values (5–9 g/d), and 22.8% had very high values (≥9 g/d). No association between urinary iodine and mean 3 × 24-h urinary sodium concentration was found (r = 0.087, P = 0.198) and UIC status did not differ according to urinary sodium categories (P = 0.804).ConclusionIn a country with mandatory universal salt iodization, consumers with salt intakes within the recommended range (<5 g/d) are iodine replete, and median UIC does not differ across categories of salt intake. This indicates that much of the dietary salt is provided from non-iodinated sources, presumably added to processed foods.     

From the Cover: Advertisements impact the physiological efficacy of a branded drug

We conducted randomized clinical trials to examine the impact of direct-to-consumer advertisements on the efficacy of a branded drug. We compared the objectively measured, physiological effect of Claritin (Merck & Co.), a leading antihistamine medication, across subjects randomized to watch a movie spliced with advertisements for Claritin or advertisements for Zyrtec (McNeil), a competitor antihistamine. Among subjects who test negative for common allergies, exposure to Claritin advertisements rather than Zyrtec advertisements increases the efficacy of Claritin. We conclude that branded drugs can interact with exposure to television advertisements.     

Combination therapy of dexamethasone with epigallocatechin enhances tibiotarsal bone articulation and modulates oxidative status correlates with cartilage cytokines expression in the early phase of experimental arthritis

The inclusion of antioxidant for the treatment of arthritis, especially under the therapy with immunosuppressant, is motivated because antioxidant plays an essential role in disease progression and moreover, immunosuppressive treatment suffers redox homeostasis balance of the organism. The aim of the present study was to evaluate the enhancement of anti-arthritic effect of dexamethasone in combination with epigallocatechin on the progression of adjuvant-induced arthritis in rats. Adjuvant arthritic rats were treated with dexamethasone (0.2 mg/kg), epigallocatechin (100 mg/kg) and combination of dexamethasone (0.1 mg/kg) with epigallocatechin (100 mg/kg) daily for a period of 28 days. Paw swelling changes, estimation of serum albumin level, alteration of bone mineral density, histopathological, and radiographical analysis were assessed to evaluate the anti-arthritic effect. Lipid peroxidation and antioxidant enzyme activities in joint tissue homogenate were performed along with the expression of different pro-inflammatory cartilage cytokines like TNF-α and IL-6. Dexamethasone and epigallocatechin combination potentiated both the antiarthritic (decrease of hind paw volume) and the antioxidant effect (lipid peroxidation, superoxide dismutase, glutathione reductase and catalase). In combination with dexamethasone, epigallocatechin markedly potentiated the beneficial effect of dexamethasone which resulted in more significant increment of serum albumin and bone mineral density. Improvement of anti-arthritic effect of combination therapy was supported by histopathological, radiographical alterations, and attenuation of over-expression of cartilage cytokines. Epigallocatechin act as potent antioxidant and combined administration of dexamethasone with epigallocatechin increased the anti-arthritic efficacy of basal dexamethasone therapy and suppressed the development phase of arthritic progression in rats.     

Teaching Medical Students About Cancer Impact Through a Longitudinal Surgical Experience: A Case Study

Background: We designed and execute a longitudinal curriculum that provides a comprehensive understanding of cancer illness and its impact upon the patient. Summary: The Harvard Medical School–Cambridge Integrated Clerkship is a redesign of the 3rd year where the traditional rotations are replaced by a single integrated year-long experience. Students are required to follow a patient with newly diagnosed gastrointestinal cancer and breast cancer, across all venues and disciplines. Twenty-nine of 34 students responded to a survey. On average patients were followed for 7 months, through 12 encounters across 4 different specialties. Students responded that this experience facilitated their understanding of cancer in a way not feasible in a traditional clerkship model. Conclusions: Medical students perceive that this longitudinal model of cancer education improves integration of the surgical, medical, scientific, emotional, and social issues. Traditional “block rotation” students and even residents are rarely afforded such an educational opportunity.     

Vertebral Venous Air Embolism: An Unusual Complication Following Colonoscopy

Although fiberoptic colonoscopy has gained wide popularity as a diagnostic and therapeutic tool, there remains an inherent complication rate following colonoscopic evaluation. Endoscopically induced bowel perforation and uncontrolled bleeding often necessitate immediate surgical intervention. Another often-unrecognized complication is the introduction of air into the vertebral venous system. A case of vertebral venous air embolism after routine diagnostic colonoscopy is reported with a review of current literature.