Receptor‐interacting protein (RIP) and Sirtuin‐3 (SIRT3) are on opposite sides of anoikis and tumorigenesis

BACKGROUND:

Regulating cross‐talk between anoikis and survival signaling pathways is crucial to regulating tissue processes and mitigating diseases like cancer. Previously, the authors demonstrated that anoikis activates a signaling pathway involving the CD95/Fas‐mediated signaling pathway that is regulated by receptor‐interacting protein (RIP), a kinase that shuttles between Fas‐mediated cell death and integrin/focal adhesion kinase (FAK)‐mediated survival pathways. Because it is known that sirtuin‐3 (SIRT3), a nicotinamide adenine dinucleotide‐dependent deacetylase, regulates cell survival, metabolism, and tumorigenesis, the authors hypothesized that SIRT3 may engage in cross‐talk with Fas/RIP/integrin/FAK survival‐death pathways in cancer cell systems.

METHODS:

Using immunohistochemical staining, immunoblotting, human tissue microarrays, and overexpression and suppression approaches in vitro and in vivo, the roles of RIP and SIRT3 were examined in oral squamous cell carcinoma (OSCC) anoikis resistance and tumorigenesis.

RESULTS:

RIP and SIRT3 had opposite expression profiles in OSCC cells and tissues. Stable suppression of RIP enhanced SIRT3 levels, whereas stable suppression of SIRT3 did not impact RIP levels in OSCC cells. The authors observed that, as OSCC cells became anoikis‐resistant, they formed multicellular aggregates or oraspheres in suspension conditions, and their expression of SIRT3 increased as their RIP expression decreased. Also, anoikis‐resistant OSCC cells with higher SIRT3 and low RIP expression induced an increased tumor burden and incidence in mice, unlike their adherent OSCC cell counterparts. Furthermore, stable suppression of SIRT3 inhibited anoikis resistance and reduced tumor incidence.

CONCLUSIONS:

The current results indicted that RIP is a likely upstream, negative regulator of SIRT3 in anoikis resistance, and an anoikis‐resistant orasphere phenotype defined by higher SIRT3 and low RIP expression contributes to a more aggressive phenotype in OSCC development. Cancer 2012. © 2012 American Cancer Society.     

Clinical Activity and Polymerase Chain Reaction Evidence of Chlamydial Infection after Repeated Mass Antibiotic Treatments for Trachoma

It is unclear how the prevalence of clinically active trachoma correlates with the prevalence of ocular chlamydial infection at the community level. In 24 villages from a cluster-randomized clinical trial of mass azithromycin distributions in Ethiopia, the correlation between the prevalence of clinical activity (on examination) and chlamydial infection (by polymerase chain reaction) was moderately strong before mass antibiotic treatments (Pearson''s correlation coefficient r = 0.75, 95% confidence interval [CI] = 0.52–0.87), but decreased at each time point during four biannual treatments (at 24 months, r = 0.15, 95% CI = −0.14–0.41). One year after the final treatment, the correlation coefficient had increased, but not to the pre-treatment level (r = 0.55, 95% CI = 0.30–0.73). In a region with hyperendemic trachoma, conjunctival examination was a useful indicator of the prevalence of chlamydial infection before treatments, less useful during mass treatments, but regained utility by one year after treatments had stopped.     

An overview of chagasic cardiomyopathy: pathogenic importance of oxidative stress

There is growing evidence to suggest that chagasic myocardia are exposed to sustained oxidative stress-induced injuries that may contribute to disease progression. Pathogen invasion- and replication-mediated cellular injuries and immune-mediated cytotoxic reactions are the common source of reactive oxygen species (ROS) in infectious etiologies. However, our understanding of the source and role of oxidative stress in chagasic cardiomyopathy (CCM) remains incomplete. In this review, we discuss the evidence for increased oxidative stress in chagasic disease, with emphasis on mitochondrial abnormalities, electron transport chain dysfunction and its role in sustaining oxidative stress in myocardium. We discuss the literature reporting the consequences of sustained oxidative stress in CCM pathogenesis.     

Maternal and Neonatal Factors Adversely Affecting Breastfeeding in the Perinatal Period

Background

Despite its known advantages, breastfeeding rates are low world over. Large number of factors affect breastfeeding. This study was designed to detect maternal and neonatal factors that adversely affect breastfeeding in the perinatal period.

Methods

A prospective, single-blinded study was conducted on randomly chosen mother-infant pairs in the maternity ward of a tertiary care service hospital. Only full term singletons born by normal vaginal delivery were studied. The B.R.E.A.S.T observation score and time spent by the infant at the mother''s breast were primary outcome variables. Maternal age, gravida, para status and education level were recorded. Birth weight, sex, gestation age of the infant and time interval from birth to observation were also recorded. Initial univariate analysis followed by multivariate analysis was performed using SPSS ver 7.5 software.

Results

A total of 54 mother-infant pairs formed the study group; 19(35.2%) were primigravidas. Primigravidas status of the mother led to significantly lower scores (p<0.04; 95% CI 0.10 to 3.62) as did maternal age < 26 years (p<0.04; 95% CI 0.2. to 3.46) on univariate analysis. Low birth weight (<2500 g) was the only neonatal factor that significantly lowered breastfeeding scores (p<0.02;95%Cl 0.56 to 6.31). On multivariate analysis only primigravida status was significantly associated with lower scores (p<0.02). The alpha value of the study was 5% and the power was 74%. Time spent by infant on breast was not significantly different between primigravida and non-primigravida mothers.

Conclusion

Primigravida status adversely affects breastfeeding scores; therefore counseling and support should be focused on this group. Extra care should also be taken to ensure adequate breastfeeding by younger mothers and in those with low birth weight infants. Larger studies with long-term follow up will be able to identify other factors and dertermine the effects of focused counseling and support in the perinatal period upon long-term breastfeeding rates.Key Words: Breastfeeding, Primigravida, Counseling     

Acute renal failure following multiple wasp stings

We report the cases of two patients who developed acute renal failure following multiple wasp stings. Both patients required dialysis and recovered within 4 weeks. The kidney biopsy from one patient showed acute tubular necrosis with interstitial nephritis. One patient had complete recovery of renal function on follow-up, while the other was lost to follow-up.     

Infected primary intramuscular echinococcosis of thigh

An unusual case of infected primary echinococcosis involving quadriceps muscles of the thigh and presenting as a cystic mass in a child is being reported. The diagnosis was made preoperatively with ultrasound examination and serology. After a cover of medical treatment the cyst was excised. Various clinical possibilities and management strategies are discussed.