Prognostic value of cardiovascular CT: is coronary artery calcium screening enough? The added value of CCTA

Coronary artery disease (CAD) is the primary cause of death in adults in the United States. Only 50% of patients who present with a myocardial infarction have a prior history of CAD. Non-invasive cardiac imaging tests have been developed to diagnose CAD. Current guidelines and systematic reviews have tried to determine the prognostic value of the coronary artery calcium (CAC) scoring and the coronary computed tomography angiography (CCTA) for major adverse cardiovascular events. Several studies support the roles of CCTA and CAC scoring for the diagnosis of CAD in asymptomatic patients. Further studies are needed to confirm the superior role of CCTA over CAC scoring in symptomatic patients.     

Correlation of Maternal Autoantibodies with Fetal Congenital Heart Block

Background

Autoimmune fetal congenital heart block (CHB) is the most severe manifestation of neonatal lupus, and it is seen when maternal autoimmune antibodies cross the placenta and damage the AV node of the fetus. CHB is mainly associated with maternal SLE with anti-Ro/SSA- and anti-La/SSB-positive status, and incidence of CHB increases when both the antibodies are present. This study was conducted to know the incidence of fetal CHB in patients of SLE who had ANA, anti-Ro/SSA and anti-La/SSB positivity.

Methods

A prospective study was conducted in a tertiary-care teaching hospital of Indian Armed Forces between Jan 2012 to Sep 2014 where 13 cases of SLE were studied. All these patients were tested for ANA, anti-Ro/SSA and anti-La/SSB antibodies and fetal heart abnormalities. Fetuses with CHB were treated with steroids.

Results

Incidence of SLE was 0.14 %, 92 % of SLE patients were positive for ANA, and 46 % had anti-Ro/SSA- and anti-La/SSB-positive status. Two fetuses had congenital heart block, and one fetus required pacemaker placement 5 months after delivery.

Conclusion

All the fetal congenital heart blocks are associated with maternal anti-Ro/SSA and anti-La/SSB and ANA antibodies. Treatment by steroids may improve the outcome in early stages of fetal CHB, and delivery with follow-up should be planned in a tertiary-care center where pacemaker placement facility is available.

     

土苓茜根汤联合阿德福韦酯治疗慢性乙肝的临床观察

目的观察土苓茜根汤联合阿德福韦酯对慢性乙型肝炎的临床疗效。方法将符合条件的慢性乙肝患者随机分为治疗组和对照组。治疗组采用土苓茜根汤联合阿德福韦酯治疗,对照组单用阿德福韦酯治疗。观察治疗前后肝功能指标及血清HBV-DNA水平的变化。结果2组治疗后肝功能指标、血清HBV-DNA水平均较治疗前下降,且治疗组较对照组改善更为明显（P<0.01）,治疗组病毒应答率高于对照组（P<0.05）。结论土苓茜根汤联合阿德福韦酯对慢性乙型肝炎具有稳定肝功能、抑制HBV-DNA复制的作用。     

Leishmania donovani-induced ceramide as the key mediator of Akt dephosphorylation in murine macrophages: role of protein kinase Czeta and phosphatase

Leishmania donovani is an intracellular protozoan parasite that impairs the host macrophage immune response to render it suitable for its survival and establishment. L. donovani-induced immunosuppression and alteration of host cell signaling is mediated by ceramide, a pleiotropic second messenger playing an important role in regulation of several kinases, including mitogen-activated protein kinase and phosphatases. We observed that the endogenous ceramide generated during leishmanial infection led to the dephosphorylation of protein kinase B (PKB) (Akt) in infected cells. The study of ceramide-mediated Akt phosphorylation revealed that Akt was dephosphorylated at both Thr308 and Ser473 sites in infected cells. Further investigation demonstrated that ceramide was also responsible for the induction of PKCzeta, an atypical Ca-independent stress kinase, as well as the ceramide-activated protein phosphatases (e.g., protein phosphatase 2A [PP2A]). We found that Akt dephosphorylation was mediated by ceramide-induced PKCzeta-Akt association and PP2A activation. In addition, treatment of L. donovani-infected macrophages with PKCzeta-specific inhibitor peptide could restore the translocation of phosphorylated Akt to the cell membrane. This study also revealed that ceramide is involved in the inhibition of proinflammatory cytokine tumor necrosis factor alpha release by infected macrophages. These observations strongly suggest the importance of ceramide in the alteration of normal cellular functions, impairment of the kinase/phosphatase balance, and thereby establishment of leishmaniasis in the hostile macrophage environment.     

Bacterial clearance of Pseudomonas aeruginosa is enhanced by the inhibition of COX-2

Prostanoids generated by COX-2 are involved in the regulation of inflammation but their exact role in the innate immune response has not been defined. We investigated whether COX-2 is involved in host defense against Pseudomonas aeruginosa pneumonia. In vitro studies, in a macrophage cell line, showed that cytotoxic strain of P aeruginosa (PA103) induced significant COX-2 protein expression and enzymatic function. In vivo data showed that infection with PA103 increased COX-2 protein production in whole lung tissue compared to mice that were infected with mutant bacteria that lack ExoU (DeltaU) or ExoU and ExoT (DeltaUT). COX-2(-/-) mice had accentuated clearance of cytotoxic P. aeruginosa from the lungs. We further tested the effects of COX-2 products such as prostaglandin E(2) on the function of phagocytic cells. Our studies indicate that prostaglandin E(2) may be involved through interacting with the EP2 receptors in modulating the host response because treatment of macrophages with prostaglandin E(2) suppressed production of reactive oxygen species. Furthermore there was enhanced bacterial clearance in EP2 receptor(-/-) mice compared to the wild-type controls. Thus it is possible that inhibition of COX-2 or EP2 receptors could be an effective adjunctive treatment for severe or resistant P. aeruginosa pneumonia.     

Phytochemical constituents,biological activities,and health‐promoting effects of the genus Origanum

Origanum species are mostly distributed around the Mediterranean, Euro‐Siberian, and Iran‐Siberian regions. Since time immemorial, the genus has popularly been used in Southern Europe, as well as on the American continent as a spice now known all over the world under the name “oregano” or “pizza‐spice.” Origanum plants are also employed to prepare bitter tinctures, wines, vermouths, beer, and kvass. The major components of Origanum essential oil are various terpenes, phenols, phenolic acids, and flavonoids with predominant occurrence of carvacrol and thymol (with reasonable amounts of p‐cymen and ‐terpinene) or of terpinene‐4‐ol, linalool, and sabinene hydrate. Many species of Origanum genus are used to treat kidney, digestive, nervous, and respiratory disorders, spasms, sore throat, diabetes, lean menstruation, hypertension, cold, insomnia, toothache, headache, epilepsy, urinary tract infections, etc. Origanum essential oil showed potent bioactivities owing to its major constituents' carvacrol, thymol, and monoterpenes. Several preclinical studies evidenced its pharmacological potential as antiproliferative or anticancer, antidiabetic, antihyperlipidemic, anti‐obesity, renoprotective, antiinflammatory, vasoprotective, cardioprotective, antinociceptive, insecticidal, and hepatoprotective properties. Its nanotechnological applications as a promising pharmaceutical in order to enhance the solubility, physicochemical stability, and the accumulation rate of its essential oils have been investigated. However, Origanum has been reported causing angioedema, perioral dermatitis, allergic reaction, inhibition of platelet aggregation, hypoglycemia, and abortion. Conclusive evidences are still required for its clinical applications against human medical conditions. Toxicity analyses and risk assessment will aid to its safe and efficacious application. In addition, elaborate structure–activity studies are needed to explore the potential use of Origanum‐derived phytochemicals as promising drug candidates.