Heat Sink Effect on Tumor Ablation Characteristics as Observed in Monopolar Radiofrequency,Bipolar Radiofrequency,and Microwave,Using Ex Vivo Calf Liver Model

Thermal ablation of liver tumors near large blood vessels is affected by the cooling effect of blood flow, leading to incomplete ablation. Hence, we conducted a comparative investigation of heat sink effect in monopolar (MP) and bipolar (BP) radiofrequency ablation (RFA), and microwave (MW) ablation devices.With a perfused calf liver, the ablative performances (volume, mass, density, dimensions), with and without heat sink, were measured. Heat sink was present when the ablative tip of the probes were 8.0 mm close to a major hepatic vein and absent when >30 mm away. Temperatures (T1 and T2) on either side of the hepatic vein near the tip of the probes, heating probe temperature (T3), outlet perfusate temperature (T4), and ablation time were monitored.With or without heat sink, BP radiofrequency ablated a larger volume and mass, compared with MP RFA or MW ablation, with latter device producing the highest density of tissue ablated. MW ablation produced an ellipsoidal shape while radiofrequency devices produced spheres.Percentage heat sink effect in Bipolar radiofrequency : Mono-polar radiofrequency : Microwave was (Volume) 33:41:22; (mass) 23:56:34; (density) 9.0:26:18; and (relative elipscity) 5.8:12.9:1.3, indicating that BP and MW devices were less affected.Percentage heat sink effect on time (minutes) to reach maximum temperature (W) = 13.28:9.2:29.8; time at maximum temperature (X) is 87:66:16.66; temperature difference (Y) between the thermal probes (T3) and the temperature (T1 + T2)/2 on either side of the hepatic vessel was 100:87:20; and temperature difference between the (T1 + T2)/2 and temperature of outlet circulating solution (T4), Z was 20.33:30.23:37.5.MW and BP radiofrequencies were less affected by heat sink while MP RFA was the most affected. With a single ablation, BP radiofrequency ablated a larger volume and mass regardless of heat sink.     

Characteristics of pediatric diabetic ketoacidosis patients in Saudi Arabia

Objectives:

To evaluate the clinical and biochemical characteristics of children with diabetic ketoacidosis (DKA).

Methods:

In this retrospective study conducted between June 2012 and November 2013 at the King Abdulaziz Medical City, Riyadh, Kingdom of Saudi Arabia, we evaluated pediatric DKA admissions from 1995-2008 (Phase 1). From the case files, we obtained information related to patients’ age, gender, weight, presenting complaints, serum biochemical profile, and management.

Results:

This study included 373 DKA admissions with a median age of 11 years (interquartile range [IQR]:8-13). The patients in the subgroup of age more than 10 years old had the highest proportion of admissions (n=250, 67%, p<0.000). The median duration of diagnosis of diabetes mellitus (DM) was 3 years (IQR:2-6). New-onset DM was 47%. Predominant precipitating cause was acute illness, mostly viral syndrome in 22% of all cases, and non-compliance to insulin regimen was in 79% of the diagnosed diabetic cases. Blood glucose, pH, anion gap, serum osmolality, serum potassium, and serum phosphate showed the highest change during the initial 6 hours of management, while trends of serum bicarbonate and blood urea nitrogen demonstrated a predominant change in the initial 12 hours.

Conclusion:

The notable findings in this study, such as, higher mean age of presentation, high rate of non-compliance to insulin as the cause of precipitation, and a high prevalence of abdominal pain at presentation should be followed up with further comparative studies.Diabetes mellitus (DM) is an endocrine disease affecting millions of children worldwide.1-3 Diabetic ketoacidosis (DKA) is one of the serious complication of diabetes in the pediatric population,4 and its prevalence increases by an annual rate of 3% worldwide.3 It is associated with significant risk of life threatening complications.5-8 The criteria for diagnosis of DKA in children by the International Society for Pediatric and Adolescent Diabetes describes DKA as blood glucose >11 mmol/L, venous pH <7.3, or bicarbonate <15 mmol/L, and ketonemia with ketonuria.9 Previous studies1,2 have reported characteristics of DKA patients based on different geographical areas. Overall, there is a paucity of literature on this particular aspect. The aim of this study was to assess pediatric patients presenting with DKA regarding aspects of demographics, presentation, investigations, and management in the Kingdom of Saudi Arabia (KSA).     

Extracellular nucleotide derivatives protect cardiomyocytes against hypoxic stress

Rationale

Extracellular nucleotides have widespread effects and various cell responses. Whereas the effect of a purine nucleotide (ATP) and a pyrimidine nucleotide (UTP) on myocardial infarction has been examined, the role of different purine and pyrimidine nucleotides and nucleosides in cardioprotection against hypoxic stress has not been reported.

Objective

To investigate the role of purine and pyrimidine nucleotides and nucleosides in protective effects in cardiomyocytes subjected to hypoxia.

Methods and results

Rat cultured cardiomyocytes were treated with various extracellular nucleotides and nucleosides, before or during hypoxic stress. The results revealed that GTP or CTP exhibit cardioprotective ability, as revealed by lactate dehydrogenase (LDH) release, by propidium iodide (PI) staining, by cell morphology, and by preserved mitochondrial activity. Pretreatment with various P2 antagonists (suramin, RB-2, or PPADS) did not abolish the cardioprotective effect of the nucleotides. Moreover, P2Y₂^−/−_, P2Y₄^−/−, and P2Y₂^−/−/P2Y₄^−/− receptor knockouts mouse cardiomyocytes were significantly protected against hypoxic stress when treated with UTP. These results indicate that the protective effect is not mediated via those receptors. We found that a wide variety of triphosphate and diphosphate nucleotides (TTP, ITP, deoxyGTP, and GDP), provided significant cardioprotective effect. GMP, guanosine, and ribose phosphate provided no cardioprotective effect. Moreover, we observed that tri/di-phosphate alone assures cardioprotection. Treatment with extracellular nucleotides, or with tri/di-phosphate, administered under normoxic conditions or during hypoxic conditions, led to a decrease in reactive oxygen species production.

Conclusions

Extracellular tri/di-phosphates are apparently the molecule responsible for cardioprotection against hypoxic damage, probably by preventing free radicals formation.     

Novel six-week protocol for generating functional human connective tissue-type (MC<Subscript>TC</Subscript>) mast cells from buffy coats

Objective

The aim of this study was to develop a novel protocol for generating large populations of fully mature and functional human mast cells (HMC) from CD34⁺ hematopoietic stem cells which require less culturing time than previously reported methods.

Methods

CD34⁺ cells isolated from fresh human buffy coats were sequentially cultured with different combinations of SCF, IL-6, IL-3, IL-9 and IL-4 under selected culturing conditions and time periods. Cells were then harvested for immunohistochemical characterization of morphological phenotypes and were functionally characterized by assessing their responses to IgE-dependent and -independent stimuli by measuring the release of inflammatory mediators and cytokines. Moreover, the pharmacological profiles of several classes of anti-inflammatory drugs in inhibiting the activation of these HMC were also characterized.

Results

We have developed a novel protocol that can generate large homogenous populations of mature and functional HMC in 6 weeks. These cells expressed both tryptase and chymase and were activated by anti-IgE, cationic peptides and calcium ionophores. Moreover, IgE-dependent activation of these cells was significantly inhibited by anti-inflammatory drugs. The morphological and functional characteristics of these mast cells resembled those of MC_TC type or connective tissue-type HMC.

Discussion

Our protocol represents a novel time-saving and economical approach for generating large numbers of primary HMC for functional studies of mast cell biology and for profiling novel anti-inflammatory therapeutic agents with mast cell-inhibitory properties in humans.

     

Endothelin-2 in ovarian follicle rupture

The ovulatory process is activated by a surge of LH, a pituitary gonadotropin, which initiates a cohort of dramatic changes in biochemical, physical, and gene expression in the ovary, leading to follicle rupture and oocyte release. Here we report the identification of endothelin-2 (EDN2) as a last moment-trigger of follicle rupture. In the ovary, EDN2 is exclusively and transiently expressed in the granulosa cells immediately before ovulation. Administration of EDN2 to the ovarian tissue induced rapid contraction, whereas addition of tezosentan, an endothelin receptor antagonist, diminishes the EDN2 effect. In vivo, treatment of tezosentan before ovulation substantially decreases gonadotropin-induced superovulation. As a target tissue of EDN2 action, we identified a layer of smooth muscle cells in the follicular wall of each follicle. Taken together, our data indicate that EDN2 induces follicular rupture by constricting periovulatory follicles.     

Mice deficient in the X-linked lymphoproliferative disease gene sap exhibit increased susceptibility to murine gammaherpesvirus-68 and hypo-gammaglobulinemia

X-linked lymphoproliferative disease is characterized by immune dysregulation and uncontrolled lymphoproliferation on exposure to Epstein-Barr virus (EBV). This disease has been attributed to mutations in the SAP gene (also denominated as SH2D1A or DSHP). To delineate the role of SAP in the pathophysiology of X-linked lymphoproliferative disease, a strain of sap-deficient mice has been generated by deleting exon 2 of the gene. After infection with murine gammaherpesvirus-68, which is homologous to EBV, the mutant mice exhibit more vigorous CD8+ T cell proliferation and more disseminated lymphocyte infiltration compared to their wild-type littermates. Chronic tissue damage and hemophagocytosis were evident in sap-deficient mice but not in their wild-type littermates. Concordantly, murine gammaherpesvirus-68 reactivation was observed in sap-deficient mice, indicating an impaired control of the virus. Notably, IgE deficiency and decreased serum IgG level were observed in mutant mice prior to and after murine gammaherpesvirus-68 infection, which reproduces hypo-gammaglobulinemia in X-linked lymphoproliferative disease patients. This mouse model will therefore be a useful tool for dissecting the various phenotypes of X-linked lymphoproliferative disease.     

Occupational exposure to asbestos and ovarian cancer: a meta-analysis

Objective: A recent Monographs Working Group of the International Agency for Research on Cancer (IARC) concluded that there is sufficient evidence for a causal association between exposure to asbestos and ovarian cancer. We performed a meta-analysis to quantitatively evaluate this association.Data sources: Searches of PubMed and unpublished data yielded a total of 18 cohort studies of women occupationally exposed to asbestos.Data extraction: Two authors independently abstracted data; any disagreement was resolved by consulting a third reviewer.Data synthesis: All but one study reported standardized mortality ratios (SMRs) comparing observed numbers of deaths with expected numbers for the general population; the exception was a study that reported standardized incidence ratios. For simplicity, we refer to all effect estimates as SMRs. The overall pooled SMR estimate for ovarian cancer was 1.77 (95% confidence interval, 1.37–2.28), with a moderate degree of heterogeneity among the studies (I² = 35.3%, p = 0.061). Effect estimates were stronger for cohorts compensated for asbestosis, cohorts with estimated lung cancer SMRs > 2.0, and studies conducted in Europe compared with other geographic regions. Effect estimates were similar for studies with and without pathologic confirmation, and we found no evidence of publication bias (Egger’s test p-value = 0.162).Conclusions: Our study supports the IARC conclusion that exposure to asbestos is associated with increased risk of ovarian cancer.