Non-alcoholic fatty liver disease (NAFLD): why you should care, when you should worry, what you should do

For the diabetologist, non-alcoholic fatty liver disease (NAFLD) is important at both ends of its spectrum. It is an early warning sign of future risk of metabolic syndrome, type 2 diabetes mellitus, and cardiovascular disease. It may also lead to late life-threatening sequela of diabetes mellitus in the event of progression to liver failure or hepatocellular carcinoma. This review will highlight the recent progress in understanding the natural history of non-alcoholic fatty liver disease and in developing a rational approach to its diagnosis, staging, and management. The pandemic prevalence of non-alcoholic fatty liver disease in Western countries necessitates both a high index of suspicion to identify cases and a non-invasive approach to staging, which is best achieved with clinical/biochemical panels and transient elastography. Lifestyle modification is the cornerstone of management. Recent clinical trials provide support for pharmacologic therapies directed at the metabolic syndrome and at protecting the liver but more data are needed. Bariatric surgery is appropriate for high-risk patients who fail conservative management. Patients with liver failure or hepatocellular carcinoma may be candidates for liver transplantation.     

Remote intervention engagement and outcomes in the Clinical Trials in Organ Transplantation in Children consortium multisite trial

Remote interventions are increasingly used in transplant medicine but have rarely been rigorously evaluated. We investigated a remote intervention targeting immunosuppressant management in pediatric lung transplant recipients. Patients were recruited from a larger multisite trial if they had a Medication Level Variability Index (MLVI) ≥2.0, indicating worrisome tacrolimus level fluctuation. The manualized intervention included three weekly phone calls and regular follow-up calls. A comparison group included patients who met enrollment criteria after the subprotocol ended. Outcomes were defined before the intent-to-treat analysis. Feasibility was defined as ≥50% of participants completing the weekly calls. MLVI was compared pre- and 180 days postenrollment and between intervention and comparison groups. Of 18 eligible patients, 15 enrolled. Seven additional patients served as the comparison. Seventy-five percent of participants completed ≥3 weekly calls; average time on protocol was 257.7 days. Average intervention group MLVI was significantly lower (indicating improved blood level stability) at 180 days postenrollment (2.9 ± 1.29) compared with pre-enrollment (4.6 ± 2.10), p = .02. At 180 days, MLVI decreased by 1.6 points in the intervention group but increased by 0.6 in the comparison group (p = .054). Participants successfully engaged in a long-term remote intervention, and their medication blood levels stabilized. NCT02266888.     

Acute injections of the NMDA receptor antagonist memantine rescue performance deficits of the Ts65Dn mouse model of Down syndrome on a fear conditioning test.

Individuals with Down syndrome (DS) and Ts65Dn mice (a major animal model of DS) carry an extra copy of the DSCR1 (Down Syndrome Critical Region 1) gene, which encodes for a protein that inhibits calcineurin. Calcineurin itself has been shown to modulate N-methyl-D-aspartate (NMDA) receptor (NMDAR) activation kinetics by decreasing channel mean open time and opening probability. We hypothesize that the overexpression of DSCR1 in persons with DS and Ts65Dn mice would inhibit normal calcineurin activity and produce pathological increases in NMDAR mean open time and opening probability. These kinetic changes should in turn produce an increase in inhibition of NMDAR-mediated currents by open channel blockers. To test this hypothesis, we investigated the locomotor-stimulating effects of MK-801 on Ts65Dn mice and have found that these mice display an increased sensitivity to this compound. Furthermore, we have found that acute injections (5 mg/kg, i.p.) of the uncompetitive NMDAR antagonist memantine rescue performance deficits of Ts65Dn mice on a fear conditioning test. Because the actions of memantine on NMDAR kinetics had been shown by others to mimic somewhat the actions of calcineurin, we attributed this positive effect of memantine on Ts65Dn mice to a drug-mediated 'normalization' of NMDAR function. To our knowledge, this is the first instance in which the acute injection of a pharmacological agent has improved the behavioral performance of Ts65Dn mice in a test of learning and memory. These results are very promising from a potential therapeutic perspective, given memantine's current status as a Food and Drug Administration (FDA)-approved drug.     

Retrospective: lessons learned from the Santa Barbara project and their implications for health information exchange

Despite its closure in December 2006, the Santa Barbara County Care Data Exchange helped focus national attention on the value of health information exchange (HIE). This in turn led to the federal government's plan to establish regional health information organizations (RHIOs). During its existence, the project pioneered innovative approaches, including certification of health information technology vendors, a community-wide governance model, and deployment of a peer-to-peer technical model now in wider use. RHIO efforts will benefit from the project's lessons about the need for an incremental development approach, rigorous implementation processes, early attention to privacy and liability concerns, and planning for a sustainable business model.     

Cadmium pathways during gestation and lactation in control versus metallothoinein 1,2-knockout mice.

Effects of metallothionein (MT) on cadmium absorption and transfer pathways during gestation and lactation in mice were investigated. Female 129/SvJ metallothionein-knockout (MT1,2KO) and metallothionein-normal (MTN) mice received drinking water containing trace amounts of (109)CdCl(2) (0.15 ng Cd/ml; 0.074 micro Ci (109)Cd/ml). (109)Cd and MT in maternal, fetal, and pup tissues were measured on gestation days 7, 14, and 17 and lactation day 11. In dams, MT influenced both the amount of (109)Cd transferred from intestine into body (two- to three-fold higher in MT1,2KO than MTN dams) and tissue-specific (109)Cd distribution (higher liver/kidney ratio in MT1,2KO dams). Placental (109)Cd concentrations in MT1,2KO dams were three- and seven-fold higher on gestation days 14 and 17, respectively, than in MTN dams. Fetal (109)Cd levels were low in both mouse types, but at least 10-fold lower in MTN fetuses. MT had no effect on the amount of (109)Cd transferred to pups via milk; furthermore, 85-90% of total pup (109)Cd was recovered in gastrointestinal tracts of both types, despite high duodenal MT only in MTN pups. A relatively large percentage of milk-derived intestinal (109)Cd was transferred to other pup tissues in both MT1,2KO and MTN pups (14 and 10%, respectively). These results demonstrate that specific sequestration of cadmium by both maternal and neonatal intestinal tract does not require MT. Although MT decreased oral cadmium transfer from intestine to body tissues at low cadmium exposure levels, MT did not play a major role in restricting transfer of cadmium from dam to fetus via placenta and to neonate via milk.     

Acute toxicity,biochemical and haematological study of Aframomum melegueta seed oil in male Wistar albino rats

Ethnopharmacological relevance

Aframomum melegueta is a popular medicinal plant in Nigeria believed to have many agents acting in different ways to bring about human health benefits. This study aimed to determine the acute toxicity, identify some phytochemicals known to be present in this plant and the possible effects on lipid profile, haematological indices and biomarker of prostate and cardiac dysfunction.

Materials and methods

Twenty four Wistar rats (284–326 g) were used in four groups of six animals. Group 1 (control) received normal saline; groups 2, 3 and 4, received intraperitoneal injection of 27.39, 54.77 and 82.16 mg/kg body weight of the extract respectively for 7 days. Haematological and biochemical parameters were measured.

Results

Alkaloids, flavonoids, saponins, tannins, cardiac glycosides, terpenoids and steroids were identified in this plant extract. The LD₅₀ was 273.86 mg/kg body weight. Prostate Specific Antigen (PSA) decreased significantly in group 2. Testosterone increased significantly in all the test groups compared to the control. Cardiac troponin I (0 ng/dl) was recorded for the test groups while the control had 1.69±0.12 ng/dl. Lipid profile results showed increase in HDL and decrease in total cholesterol and LDL-cholesterol. Haemoglobin (Hb) and Red Blood Cells count (RBC) decreased significantly in group 4. White Blood Cells count (WBC), Mean Cell Volume (MCV), Mean Cell Haemoglobin (MCH) and Mean Cell Haemoglobin Concentration (MCHC) did not change significantly.

Conclusion

Aframomum melegueta seed oil has the potential of ameliorating benign prostatic hyperplasia (BPH) and cardiac dysfunction as indicated by testosterone, PSA, lipid profile and troponin I levels. The LD₅₀ of 273.86 mg/kg body weight is indicative of mild toxicity. The lower than normal Hb, RBC confirms the possibility of toxicity.