The effects of HIV protease inhibitors atazanavir and lopinavir/ritonavir on insulin sensitivity in HIV-seronegative healthy adults

BACKGROUND: Therapy with some HIV protease inhibitors (PI) contributes to insulin resistance and type 2 diabetes mellitus, by inhibition of insulin-sensitive glucose transporters. Atazanavir (ATV) is a new PI with substantially less in vitro effect on glucose transport than observed with other PI, including lopinavir (LPV) or ritonavir (RTV). METHODS: Randomized, double-blind, crossover study of the effect of 5 days of administering ATV, lopinavir/ritonavir (LPV/r) or placebo on insulin-stimulated glucose disposal in 30 healthy HIV-negative subjects. Each subject was studied on two of three possible treatments with a wash-out period between treatments. RESULTS: The mean insulin-stimulated glucose disposal (mg/min per kg body weight) per unit insulin (microU/ml) (M/I) was 9.88, 9.80 and 7.52 for placebo, ATV and LPV/r, respectively (SEM, 0.84 for all). There was no significant difference between ATV and placebo. The M/I for LPV/r was 23% lower than that for ATV (P = 0.010) and 24% lower than that for placebo (P = 0.008). The mean glycogen storage rates were 3.85, 4.00 and 2.54 mg/min per kg for placebo, ATV and LPV/r, respectively (SEM, 0.39 for all). There was no significant difference between ATV and placebo. The glycogen storage rate for LPV/r was 36% lower than ATV (P = 0.003) and 34% lower than placebo (P = 0.006). CONCLUSIONS: ATV given to healthy subjects for 5 days did not affect insulin sensitivity, while LPV/r induced insulin resistance. This observation is consistent with differential in vitro effects of these PI on glucose transport. Further data are needed to assess clinical implications for body composition.     

Transcatheter Aortic Valve Implantation: Bahrain Experience

BACKGROUNDTranscatheter aortic valve implantation (TAVI) is a minimally invasive procedure that is considered a good alternative to surgical aortic valve replacement (sAVR) in selected patients. Our aim is to determine the baseline, procedural characteristics and one-year clinical outcomes of our TAVI registry.METHODSThis study is a retrospective observational analysis of a prospectively designed cohort comprising 81 consecutive patients treated at Mohammed bin Khalifa Cardiac Centre (MKCC) who were enrolled in Bahrain TAVI registry from February 2014 to February 2019. The clinical endpoints were defined according to the updated Valve Academic Research Consortium-2 (VARC-2) consensus document.RESULTSOut of the 81 patients included in our study, there were 37 (45.7%) males. The mean age was 76.4 ± 8.9 years with a mean Logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE II) of 4.1 ± 2.5 and a mean Society of Thoracic Surgery (STS) Risk Score of 4.2 ± 3.5. Evolute-R valve was used for 36 (44.4%) patients, Edward Sapien for 26 patients (32.1%), and Core valve for 19 patients (23.5%). At one year follow up, all-cause death was reported in three (3.7%) patients; none of them was cardiovascular mortality. As per VARC-II criteria, no cases fulfilled the criteria of valve dysfunction but TAVI-related complications (i.e., TAV-in-TAV deployment) were reported in four (4.9%) cases. One (1.2%) case of major bleeding was encountered but no patient experienced life-threatening bleeding. Major vascular complications were documented in two patients (2.5%) only. Significant Acute Kidney Injury (AKI) occurred in two (2.5%) patients, both classified as stage-2 but no one deteriorated to stage-3 or hemodialysis. Seven (8.6%) patients required permanent pacemakers, and all were implanted during the index admission for TAVI. One patient (1.2%) had stroke and all survivors completed one-year follow up.CONCLUSIONThe TAVI program in Bahrain is encouraging and corresponds to the finest international centers outcomes in terms of procedural success and complications rate.     

Osteonecrosis of the jaw in a Crohn’s disease patient following a course of Bisphosphonate and Adalimumab therapy: a case report

Background

Cyclooxygenase-2 (COX-2, PTGS2) is an enzyme involved in the synthesis of prostaglandins and thromboxanes, which are regulators of biologic processes such as inflammation, cell proliferation and angiogenesis. COX-2 over-expression was reported in many (pre) malignant tissues, but data strongly vary and seem to depend on the methodology used.

Methods

Normal colorectal mucosa and paired cancerous tissue from 60 patients with colorectal cancer was investigated for the levels of COX-2 mRNA by real-time quantitative Polymerase Chain Reaction (qPCR). COX-2 levels were expressed relative to either: tissue weight or levels of the housekeeping genes beta-2 microglobulin (B2M) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH).

Results

COX-2 mRNA levels, normalized with respect to tissue weight or mRNA levels of the housekeeping genes B2M or GAPDH, were over-expressed in 80%, 70% and 40% of the colorectal tumor tissues, as compared to the paired adjacent normal colorectal mucosa samples, respectively. Highest mRNA COX-2 ratios tumor/normal were measured when expressed per mg tissue (mean ratio 21.6). When normalized with respect to the housekeeping genes B2M or GAPDH, mean tumor/normal ratios were 16.1 and 7.5, respectively.

Conclusion

Expression of COX-2 mRNA levels per mg tissue is most simple in comparison to normalization with respect to the housekeeping genes B2M or GAPDH. Levels of COX-2 mRNA are found over-expressed in almost 80% of the colorectal tumors, compared to paired adjacent normal colorectal mucosa, suggesting a role of COX-2 as a potential biomarker for cancer risk, whereas inhibitors of COX-2 could be of value in chemoprevention of colon cancer.     

Magnetic and Tunable Sound Absorption Properties of an In-Situ Prepared Magnetorheological Foam

Conventional polyurethane foam has non-tunable sound absorption properties. Here, a magneto-induced foam, called magnetorheological (MR) foam, was fabricated with the feature of being able to tune sound absorption properties, primarily from the middle- to higher-frequency ranges. Three different samples of MR foams were fabricated in situ by varying the concentration of Carbonyl Iron Particles (CIPs) (0, 35, and 75 wt.%). The magnetization properties and tunable sound absorption characteristics were evaluated. From the magnetic saturation properties, the results showed very narrow and small coercivity of hysteresis loops relative to the soft magnetic properties of the CIPs. MR foam with 75 wt.% CIPs showed a higher magnetic saturation at 91.350 emu/g compared to MR foam with 35 wt.% CIPs at 63.896 emu/g. For tunable sound absorption testing, the effect of ‘shifting’ to higher frequency was also observed when the magnetic field was applied, which was ~10 Hz for MR foam with 35 wt.% CIPs and ~130 Hz for MR foam with 75 wt.% CIPs. As the latest evolution of semi-active noise control materials, the results from this study are valuable guidance for the advancement of MR-based devices.